合成生物学

来自集智百科 - 伊辛模型
跳到导航 跳到搜索

此词条暂由袁一博翻译,翻译字数共4491,未经人工整理和审校,带来阅读不便,请见谅。

模板:Redirect

模板:Synthetic biology

文件:Synthetic Biology Research at NASA Ames.jpg
Synthetic Biology Research at NASA Ames Research Center. NASA埃姆斯研究中心的合成生物学研究。

NASA Ames Research Center.]]

美国国家航空和宇宙航行局/美国国家航空航天局埃姆斯研究中心


Synthetic biology (SynBio) is a multidisciplinary area of research that seeks to create new biological parts, devices, and systems, or to redesign systems that are already found in nature.

Synthetic biology (SynBio) is a multidisciplinary area of research that seeks to create new biological parts, devices, and systems, or to redesign systems that are already found in nature.

合成生物学(SynBio,Synthetic biology)是一门综合性的自然学科,旨在创造新的生物部件(Part)、生物装置(Device)和生物系统(System),或对自然界中已经存在的生物系统进行重新设计。


It is a branch of science that encompasses a broad range of methodologies from various disciplines, such as biotechnology, genetic engineering, molecular biology, molecular engineering, systems biology, membrane science, biophysics, chemical and biological engineering, electrical and computer engineering, control engineering and evolutionary biology.

It is a branch of science that encompasses a broad range of methodologies from various disciplines, such as biotechnology, genetic engineering, molecular biology, molecular engineering, systems biology, membrane science, biophysics, chemical and biological engineering, electrical and computer engineering, control engineering and evolutionary biology.

合成生物学是科学的一个分支,囊括了多种学科的广泛性方法论,如生物技术,遗传工程,分子生物学,分子工程,系统生物学,脂双层膜的膜科学,生物物理学,化学和生物工程,电子和计算机工程,控制工程和进化生物学。


Due to more powerful genetic engineering capabilities and decreased DNA synthesis and sequencing costs, the field of synthetic biology is rapidly growing. In 2016, more than 350 companies across 40 countries were actively engaged in synthetic biology applications; all these companies had an estimated net worth of $3.9 billion in the global market.[1]

Due to more powerful genetic engineering capabilities and decreased DNA synthesis and sequencing costs, the field of synthetic biology is rapidly growing. In 2016, more than 350 companies across 40 countries were actively engaged in synthetic biology applications; all these companies had an estimated net worth of $3.9 billion in the global market.

随着遗传工程(即基因工程)能力越来越强大和DNA 合成及测序成本的逐渐降低,合成生物学领域正在迅速发展。2016年,来自40个国家的350多家公司积极致力于合成生物学的应用领域,这些公司在全球市场的估计净值总额为39亿美元。


Definition 定义

Synthetic biology currently has no generally accepted definition. Here are a few examples:

Synthetic biology currently has no generally accepted definition. Here are a few examples:

合成生物学目前还没有公认的定义。以下是一些定义的示例:


  • "the use of a mixture of physical engineering and genetic engineering to create new (and, therefore, synthetic) life forms" [2]

“联合使用物理工程和基因工程来创建新的(因而也即合成的)生命形式。”[3]

  • "an emerging field of research that aims to combine the knowledge and methods of biology, engineering and related disciplines in the design of chemically synthesized DNA to create organisms with novel or enhanced characteristics and traits" “一个新兴的研究领域,旨在将生物学、工程学和设计化学合成DNA 的相关学科的知识和方法结合起来,用于创造具有新颖或增强特征和形状的新生物。”[4]
  • "designing and constructing biological modules, biological systems, and biological machines or, re-design of existing biological systems for useful purposes" “设计和构建生物模块(生物积木)、生物系统以及生物机器,或以有用为目的重新设计现有的生物系统。” [5]


  • "applying the engineering paradigm of systems design to biological systems in order to produce predictable and robust systems with novel functionalities that do not exist in nature (The European Commission, 2005)This can include the possibility of a molecular assembler, based upon biomolecular systems such as the ribosome " “将系统设计的工程范式应用到生物系统中,用于产生可预测的和具有鲁磁性(robust)的新生物系统,后者在自然界中并不存在。(欧洲委员会,2005年)这可能包括基于生物分子系统——例如核糖体——的分子组合器的可能性。”[6]



To note, synthetic biology has traditionally been divided into two different approaches: top down and bottom up.

To note, synthetic biology has traditionally been divided into two different approaches: top down and bottom up.

值得注意的是,合成生物学在传统上被分为两种不同的方法: 自上而下和自下而上。


  1. The top down approach involves using metabolic and genetic engineering techniques to impart new functions to living cells.
The top down approach involves using metabolic and genetic engineering techniques to impart new functions to living cells.

自上而下的方法包括利用代谢和基因工程技术赋予活细胞以新的功能。

  1. The bottom up approach involves creating new biological systems in vitro by bringing together 'non-living' biomolecular components,[7] often with the aim of constructing an artificial cell.
The bottom up approach involves creating new biological systems in vitro by bringing together 'non-living' biomolecular components, often with the aim of constructing an artificial cell.

自下而上的方法包括在体外创建新的生物系统,将“非活性”的生物分子组件聚集在一起,其目的通常是构建一个人工细胞。


Biological systems are thus assembled module-by-module. Cell-free protein expression systems are often employed,[8][9][10] as are membrane-based molecular machinery. There are increasing efforts to bridge the divide between these approaches by forming hybrid living/synthetic cells,[11] and engineering communication between living and synthetic cell populations.[12]

Biological systems are thus assembled module-by-module. Cell-free protein expression systems are often employed, as are membrane-based molecular machinery. There are increasing efforts to bridge the divide between these approaches by forming hybrid living/synthetic cells, and engineering communication between living and synthetic cell populations.

生物系统就是这样一个模块一个模块地组装起来的。无细胞蛋白表达系统作为以膜为基础的分子机制,经常被采用。通过形成活细胞/合成细胞的混合体,以及在活细胞和合成细胞群之间进行工程交流,科学家前赴后继地努力为这些系统之间架起桥梁。


History 发展历程

1910: First identifiable use of the term "synthetic biology" in Stéphane Leduc's publication Théorie physico-chimique de la vie et générations spontanées.[13] He also noted this term in another publication, La Biologie Synthétique in 1912.[14]

1910: First identifiable use of the term "synthetic biology" in Stéphane Leduc's publication Théorie physico-chimique de la vie et générations spontanées. He also noted this term in another publication, La Biologie Synthétique in 1912.

1910: First identifiable use of the term "synthetic biology" in Stéphane Leduc's publication Théorie physico-chimique de la vie et générations spontanées.他还在1912年的另一本出版物《生物合成学》中提到了这个术语。


1961: Jacob and Monod postulate cellular regulation by molecular networks from their study of the lac operon in E. coli and envisioned the ability to assemble new systems from molecular components.[15]

1961: Jacob and Monod postulate cellular regulation by molecular networks from their study of the lac operon in E. coli and envisioned the ability to assemble new systems from molecular components.

1961年: 雅各布和莫诺德通过他们对大肠杆菌中乳酸操纵子的研究,设想了通过分子网络调控细胞的方法,并预期了由分子组件组装新系统的能力。


1973: First molecular cloning and amplification of DNA in a plasmid is published in P.N.A.S. by Cohen, Boyer et al. constituting the dawn of synthetic biology.[16] 1973: First molecular cloning and amplification of DNA in a plasmid is published in P.N.A.S. by Cohen, Boyer et al. constituting the dawn of synthetic biology.

1973年:第一篇关于质粒中 DNA 的分子克隆和扩增的文章在 P.N.A.S. 发表。作者: 科恩,波义耳等人(Cohen,Boyer et al.) 。构成了合成生物学的黎明


1978: Arber, Nathans and Smith win the Nobel Prize in Physiology or Medicine for the discovery of restriction enzymes, leading Szybalski to offer an editorial comment in the journal Gene:

1978: Arber, Nathans and Smith win the Nobel Prize in Physiology or Medicine for the discovery of restriction enzymes, leading Szybalski to offer an editorial comment in the journal Gene:

1978年: 阿尔伯 (Arber) ,纳森斯 (Nathans) 和 史密斯 (Smith) 因为限制性内切酶的发现而获得美国诺贝尔生理学或医学奖学会奖,这使得齐巴尔斯基 (Szybalski) 在《基因》杂志上发表了一篇社论评论:


The work on restriction nucleases not only permits us easily to construct recombinant DNA molecules and to analyze individual genes, but also has led us into the new era of synthetic biology where not only existing genes are described and analyzed but also new gene arrangements can be constructed and evaluated.[17]

The work on restriction nucleases not only permits us easily to construct recombinant DNA molecules and to analyze individual genes, but also has led us into the new era of synthetic biology where not only existing genes are described and analyzed but also new gene arrangements can be constructed and evaluated.

限制性核酸酶的研究不仅使我们能够很容易地构建重组 DNA 分子和分析单个基因,而且使我们进入了合成生物学的新时代,不仅可以描述和分析现有的基因,而且可以构建和评估新的基因序列。


1988: First DNA amplification by the polymerase chain reaction (PCR) using a thermostable DNA polymerase is published in Science by Mullis et al.[18] This obviated adding new DNA polymerase after each PCR cycle, thus greatly simplifying DNA mutagenesis and assembly. 1988: First DNA amplification by the polymerase chain reaction (PCR) using a thermostable DNA polymerase is published in Science by Mullis et al. This obviated adding new DNA polymerase after each PCR cycle, thus greatly simplifying DNA mutagenesis and assembly.

1988年: 第一次利用热稳定的 DNA 聚合酶进行聚合酶链式反应以实现 DNA 扩增(PCR)的成果由马利斯 (Mullis) 等人发表在《科学》杂志上,这样就避免了在每次 PCR 循环后增加新的 DNA 聚合酶,从而大大简化了 DNA 的突变和组装。


2000: Two papers in Nature report synthetic biological circuits, a genetic toggle switch and a biological clock, by combining genes within E. coli cells.[19][20]

2000: Two papers in Nature report synthetic biological circuits, a genetic toggle switch and a biological clock, by combining genes within E. coli cells.

2000年: 《自然》杂志的两篇论文报告了通过结合大肠杆菌细胞内的基因制造合成生物电路、基因切换开关和生物钟。


2003: The most widely used standardized DNA parts, BioBrick plasmids, are invented by Tom Knight.[21] These parts will become central to the international Genetically Engineered Machine competition (iGEM) founded at MIT in the following year.

2003: The most widely used standardized DNA parts, BioBrick plasmids, are invented by Tom Knight. These parts will become central to the international Genetically Engineered Machine competition (iGEM) founded at MIT in the following year.

2003年: 最广泛使用的标准化 DNA 部件,生物积木质粒,是由汤姆·奈特 (Tom Knight) 发明的。这些部分将成为2004年在麻省理工学院成立的国际基因工程机器竞赛 (iGEM) 的中心。


Synthetic Biology Open Language (SBOL) standard visual symbols for use with BioBricks Standard

[与生物积木标准一起使用的合成生物学开放式语言(SBOL)标准视觉符号]


2003: Researchers engineer an artemisinin precursor pathway in E. coli.[22]

2003: Researchers engineer an artemisinin precursor pathway in E. coli.

2003年: 研究人员在大肠杆菌中设计出青蒿素前体途径。


2004: First international conference for synthetic biology, Synthetic Biology 1.0 (SB1.0) is held at the Massachusetts Institute of Technology, USA.

2004: First international conference for synthetic biology, Synthetic Biology 1.0 (SB1.0) is held at the Massachusetts Institute of Technology, USA.

2004年: 第一届合成生物学国际会议,合成生物学1.0(SB1.0)在美国麻省理工学院举行。


2005: Researchers develop a light-sensing circuit in E. coli.[23] Another group designs circuits capable of multicellular pattern formation.[24]

2005: Researchers develop a light-sensing circuit in E. coli. Another group designs circuits capable of multicellular pattern formation.

2005年: 研究人员在大肠杆菌中开发出一种感光电路。另一个研究小组设计出了能够形成多细胞模式的电路。


2006: Researchers engineer a synthetic circuit that promotes bacterial invasion of tumour cells.[25]

2006: Researchers engineer a synthetic circuit that promotes bacterial invasion of tumour cells.

2006年: 研究人员设计了一种能促进细菌侵入肿瘤细胞的合成电路。


2010: Researchers publish in Science the first synthetic bacterial genome, called M. mycoides JCVI-syn1.0.[26][27] The genome is made from chemically-synthesized DNA using yeast recombination.

2010: Researchers publish in Science the first synthetic bacterial genome, called M. mycoides JCVI-syn1.0. The genome is made from chemically-synthesized DNA using yeast recombination.

2010年: 研究人员在《科学》杂志上发表了第一个人工合成的细菌基因组,名为丝状支原体 JCVI-syn1.0。基因组是使用酵母由化学合成的 DNA重组得到的。


2011: Functional synthetic chromosome arms are engineered in yeast.[28]

2011: Functional synthetic chromosome arms are engineered in yeast.

2011年: 成功在酵母中设计出功能性合成染色体臂。


2012: Charpentier and Doudna labs publish in Science the programming of CRISPR-Cas9 bacterial immunity for targeting DNA cleavage.[29] This technology greatly simplified and expanded eukaryotic gene editing. 2012: Charpentier and Doudna labs publish in Science the programming of CRISPR-Cas9 bacterial immunity for targeting DNA cleavage. This technology greatly simplified and expanded eukaryotic gene editing.

2012年: Charpentier 和 Doudna 实验室在《科学》杂志上发表了 CRISPR-Cas9细菌免疫系统的程序设计,用于靶向 DNA 的裂解。这项技术极大地简化和扩展了真核生物的基因编辑。


2019: Scientists at ETH Zurich report the creation of the first bacterial genome, named Caulobacter ethensis-2.0, made entirely by a computer, although a related viable form of C. ethensis-2.0 does not yet exist.[30][31]

2019: Scientists at ETH Zurich report the creation of the first bacterial genome, named Caulobacter ethensis-2.0, made entirely by a computer, although a related viable form of C. ethensis-2.0 does not yet exist.

2019年: 苏黎世联邦理工学院 (ETH Zurich) 的科学家报告说,他们已经创造出了第一个细菌基因组,并将其命名为 Caulobacter ethensis-2.0 ,这个基因组完全是由计算机制造的,尽管与之相关的可存活的Caulobacter ethensis-2.0还不存在。


2019: Researchers report the production of a new synthetic (possibly artificial) form of viable life, a variant of the bacteria Escherichia coli, by reducing the natural number of 64 codons in the bacterial genome to 59 codons instead, in order to encode 20 amino acids.[32][33]

2019: Researchers report the production of a new synthetic (possibly artificial) form of viable life, a variant of the bacteria Escherichia coli, by reducing the natural number of 64 codons in the bacterial genome to 59 codons instead, in order to encode 20 amino acids.

2019年: 研究人员报告了一种新式合成(可能是人工的)可行生命形式的产生,这是大肠杆菌的变种,它通过将细菌基因组中64个密码子的自然数目减少到59个密码子来编码20个氨基酸。


Perspectives 各方观点

Engineers view biology as a technology (in other words, a given system's biotechnology or its biological engineering)[34] Synthetic biology includes the broad redefinition and expansion of biotechnology, with the ultimate goals of being able to design and build engineered biological systems that process information, manipulate chemicals, fabricate materials and structures, produce energy, provide food, and maintain and enhance human health (see Biomedical Engineering) and our environment.[35]

Engineers view biology as a technology (in other words, a given system's biotechnology or its biological engineering) Synthetic biology includes the broad redefinition and expansion of biotechnology, with the ultimate goals of being able to design and build engineered biological systems that process information, manipulate chemicals, fabricate materials and structures, produce energy, provide food, and maintain and enhance human health (see Biomedical Engineering) and our environment.

工程师将生物学视为一种技术(换句话说,一个特定系统的生物技术或其生物工程)合成生物学包括生物技术的广泛重新定义和扩展,最终目标是能够设计和建造工程生物系统,处理信息,操纵化学品,制造材料和结构,生产能源,提供食物,维护和增强人类健康(见生物医学工程)和我们的环境。


Studies in synthetic biology can be subdivided into broad classifications according to the approach they take to the problem at hand: standardization of biological parts, biomolecular engineering, genome engineering. [citation needed]

Studies in synthetic biology can be subdivided into broad classifications according to the approach they take to the problem at hand: standardization of biological parts, biomolecular engineering, genome engineering.

合成生物学的研究可以根据它们对手头问题所采取的方法再广泛细分为: 生物部分的标准化、生物分子工程、基因组工程。


Biomolecular engineering includes approaches that aim to create a toolkit of functional units that can be introduced to present new technological functions in living cells. Genetic engineering includes approaches to construct synthetic chromosomes for whole or minimal organisms.

Biomolecular engineering includes approaches that aim to create a toolkit of functional units that can be introduced to present new technological functions in living cells. Genetic engineering includes approaches to construct synthetic chromosomes for whole or minimal organisms.

生物分子工程包括旨在创建一个功能单元工具包的方法,这些功能单元可以用来展示活细胞中的新技术性功能。基因工程包括为整个或最小的有机体构建合成染色体的方法。


Biomolecular design refers to the general idea of de novo design and additive combination of biomolecular components. Each of these approaches share a similar task: to develop a more synthetic entity at a higher level of complexity by inventively manipulating a simpler part at the preceding level.[36]

Biomolecular design refers to the general idea of de novo design and additive combination of biomolecular components. Each of these approaches share a similar task: to develop a more synthetic entity at a higher level of complexity by inventively manipulating a simpler part at the preceding level.

生物分子设计是指生物分子组分的重新设计和加合的总体思想。这些方法都有一个相似的任务: 通过在前一级创造性地操作一个更简单的部分,从而在更高的复杂性水平上开发一个更高度合成化的实体。


On the other hand, "re-writers" are synthetic biologists interested in testing the irreducibility of biological systems. Due to the complexity of natural biological systems, it would be simpler to rebuild the natural systems of interest from the ground up; In order to provide engineered surrogates that are easier to comprehend, control and manipulate.[37] Re-writers draw inspiration from refactoring, a process sometimes used to improve computer software.

On the other hand, "re-writers" are synthetic biologists interested in testing the irreducibility of biological systems. Due to the complexity of natural biological systems, it would be simpler to rebuild the natural systems of interest from the ground up; In order to provide engineered surrogates that are easier to comprehend, control and manipulate. Re-writers draw inspiration from refactoring, a process sometimes used to improve computer software.

另一方面,“重写者”指的是对测试生物系统的不可还原性感兴趣的合成生物学家。由于自然生物系统的复杂性,从头开始重建感兴趣的自然系统会更简单; 为了提供更容易理解、控制和操作的工程替代品。重写者从重构中获得灵感,我们有时用这种重构以改进计算机软件。


Enabling technologies 使能技术

Several novel enabling technologies were critical to the success of synthetic biology. Concepts include standardization of biological parts and hierarchical abstraction to permit using those parts in synthetic systems.[38] Basic technologies include reading and writing DNA (sequencing and fabrication). Measurements under multiple conditions are needed for accurate modeling and computer-aided design (CAD).

Several novel enabling technologies were critical to the success of synthetic biology. Concepts include standardization of biological parts and hierarchical abstraction to permit using those parts in synthetic systems. Basic technologies include reading and writing DNA (sequencing and fabrication). Measurements under multiple conditions are needed for accurate modeling and computer-aided design (CAD).

一些新的使能技术对于合成生物学的成功至关重要。它的概念囊括了生物部分的标准化和层次抽象,以允许在合成系统中使用这些部分。基本技术包括读写 DNA (测序和编码)。为了精确地建模和计算机辅助设计(CAD) ,需要在多种条件下进行测量。


DNA and gene synthesis DNA 和基因合成

Driven by dramatic decreases in costs of oligonucleotide ("oligos") synthesis and the advent of PCR, the sizes of DNA constructions from oligos have increased to the genomic level.[39] In 2000, researchers reported synthesis of the 9.6 kbp (kilo bp) Hepatitis C virus genome from chemically synthesized 60 to 80-mers.[40] In 2002 researchers at Stony Brook University succeeded in synthesizing the 7741 bp poliovirus genome from its published sequence, producing the second synthetic genome, spanning two years.[41] In 2003 the 5386 bp genome of the bacteriophage Phi X 174 was assembled in about two weeks.[42] In 2006, the same team, at the J. Craig Venter Institute, constructed and patented a synthetic genome of a novel minimal bacterium, Mycoplasma laboratorium and were working on getting it functioning in a living cell.[43][44][45]

Driven by dramatic decreases in costs of oligonucleotide ("oligos") synthesis and the advent of PCR, the sizes of DNA constructions from oligos have increased to the genomic level. In 2000, researchers reported synthesis of the 9.6 kbp (kilo bp) Hepatitis C virus genome from chemically synthesized 60 to 80-mers. In 2002 researchers at Stony Brook University succeeded in synthesizing the 7741 bp poliovirus genome from its published sequence, producing the second synthetic genome, spanning two years. In 2003 the 5386 bp genome of the bacteriophage Phi X 174 was assembled in about two weeks. In 2006, the same team, at the J. Craig Venter Institute, constructed and patented a synthetic genome of a novel minimal bacterium, Mycoplasma laboratorium and were working on getting it functioning in a living cell.

由于寡核苷酸 (oligos) 合成成本的大幅度降低和 PCR 的出现,寡核苷酸 DNA 构建的大小已经提高到基因组水平。2000年,研究人员报道了化学合成的60到80碱基数的聚丙型肝炎病毒基因组的合成。2002年,石溪大学的研究人员成功地从已发表的序列中合成了7741碱基数的脊髓灰质炎病毒基因组,生产了跨越两年的第二个合成基因组。2003年,噬菌体 Phi x 174的5386个基因组在大约两周内组装完毕。2006年,克莱格·凡特 (J. Craig Venter) 研究所的同一个团队,构建了一种新型微型细菌——支原体的合成基因组,并申请了专利,他们正在努力使其在活细胞中发挥作用。


In 2007 it was reported that several companies were offering synthesis of genetic sequences up to 2000 base pairs (bp) long, for a price of about $1 per bp and a turnaround time of less than two weeks.[46] Oligonucleotides harvested from a photolithographic- or inkjet-manufactured DNA chip combined with PCR and DNA mismatch error-correction allows inexpensive large-scale changes of codons in genetic systems to improve gene expression or incorporate novel amino-acids (see George M. Church's and Anthony Forster's synthetic cell projects.[47][48]) This favors a synthesis-from-scratch approach.

In 2007 it was reported that several companies were offering synthesis of genetic sequences up to 2000 base pairs (bp) long, for a price of about $1 per bp and a turnaround time of less than two weeks. Oligonucleotides harvested from a photolithographic- or inkjet-manufactured DNA chip combined with PCR and DNA mismatch error-correction allows inexpensive large-scale changes of codons in genetic systems to improve gene expression or incorporate novel amino-acids (see George M. Church's and Anthony Forster's synthetic cell projects.) This favors a synthesis-from-scratch approach.

2007年有报道称,几家公司提供了长达2000个碱基对的基因序列合成,价格约为每个碱基1美元,一个完整流程所需工时不到两周。从光刻或喷墨制造的 DNA 芯片中提取的寡核苷酸,结合 PCR 和 DNA 错配错误校正,可以大规模改变遗传系统中的密码子,从而改善基因表达或合并新的氨基酸(参见乔治·M·丘奇和安东尼·福斯特的合成细胞项目)这有利于采用从头开始的合成方法。


Additionally, the CRISPR/Cas system has emerged as a promising technique for gene editing. It was described as "the most important innovation in the synthetic biology space in nearly 30 years".[49] While other methods take months or years to edit gene sequences, CRISPR speeds that time up to weeks.[49] Due to its ease of use and accessibility, however, it has raised ethical concerns, especially surrounding its use in biohacking.[50][51][52]

Additionally, the CRISPR/Cas system has emerged as a promising technique for gene editing. It was described as "the most important innovation in the synthetic biology space in nearly 30 years". While other methods take months or years to edit gene sequences, CRISPR speeds that time up to weeks.

此外,CRISPR/Cas 系统已经成为一种很有前途的基因编辑技术。它被称作“近30年来合成生物学领域最重要的创新”。虽然其他方法需要数月或数年来编辑基因序列,CRISPR 将这个时间缩短到数周。


Sequencing 测序

DNA sequencing determines the order of nucleotide bases in a DNA molecule. Synthetic biologists use DNA sequencing in their work in several ways. First, large-scale genome sequencing efforts continue to provide information on naturally occurring organisms. This information provides a rich substrate from which synthetic biologists can construct parts and devices. Second, sequencing can verify that the fabricated system is as intended. Third, fast, cheap, and reliable sequencing can facilitate rapid detection and identification of synthetic systems and organisms.[53]

DNA sequencing determines the order of nucleotide bases in a DNA molecule. Synthetic biologists use DNA sequencing in their work in several ways. First, large-scale genome sequencing efforts continue to provide information on naturally occurring organisms. This information provides a rich substrate from which synthetic biologists can construct parts and devices. Second, sequencing can verify that the fabricated system is as intended. Third, fast, cheap, and reliable sequencing can facilitate rapid detection and identification of synthetic systems and organisms.

DNA 测序决定了 DNA 分子中核苷酸碱基的顺序。合成生物学家在他们的工作中以几种方式使用 DNA 测序。首先,大规模的基因组测序工作继续提供有关自然发生的生物体的信息。这些信息为合成生物学家提供了一个丰富的基质,他们可以从中构建零件和设备。其次,排序可以验证制造的系统是否如预期的那样。第三,快速、廉价和可靠的测序可以促进快速检测和识别合成系统和有机体。


Microfluidics

Microfluidics, in particular droplet microfluidics, is an emerging tool used to construct new components, and to analyse and characterize them.[54][55] It is widely employed in screening assays.[56]

Microfluidics, in particular droplet microfluidics, is an emerging tool used to construct new components, and to analyse and characterize them. It is widely employed in screening assays.

微流体,特别是液滴微流体,是一种新兴的工具,常用于构造新的元件,并分析和表征它们。它被广泛应用于筛选分析。


Modularity 模块化

The most used[57]:22–23 standardized DNA parts are BioBrick plasmids, invented by Tom Knight in 2003.[58] Biobricks are stored at the Registry of Standard Biological Parts in Cambridge, Massachusetts. The BioBrick standard has been used by thousands of students worldwide in the international Genetically Engineered Machine (iGEM) competition.[57]:22–23

The most used standardized DNA parts are BioBrick plasmids, invented by Tom Knight in 2003. Biobricks are stored at the Registry of Standard Biological Parts in Cambridge, Massachusetts. The BioBrick standard has been used by thousands of students worldwide in the international Genetically Engineered Machine (iGEM) competition. SH3 domain-peptide binding or SpyTag/SpyCatcher offer such control. In addition it is necessary to regulate protein-protein interactions in cells, such as with light (using light-oxygen-voltage-sensing domains) or cell-permeable small molecules by chemically induced dimerization.

最常用的标准化 DNA 部分是生物积木质粒,由汤姆·奈特在2003年发明。生物积木储存在马萨诸塞州剑桥的标准生物部件注册处。生物积木标准已经被全世界成千上万的学生应用于国际基因工程机器竞赛 (iGEM) 。SH3域-肽结合或 SpyTag/SpyCatcher 能提供这样的控制。此外,还必须通过化学诱导的二聚化来调节细胞中蛋白质-蛋白质的相互作用,例如利用光(光-氧-电压感应域)或细胞渗透性小分子。


While DNA is most important for information storage, a large fraction of the cell's activities are carried out by proteins. Tools can send proteins to specific regions of the cell and to link different proteins together. The interaction strength between protein partners should be tunable between a lifetime of seconds (desirable for dynamic signaling events) up to an irreversible interaction (desirable for device stability or resilient to harsh conditions). Interactions such as coiled coils,[59] SH3 domain-peptide binding[60] or SpyTag/SpyCatcher[61] offer such control. In addition it is necessary to regulate protein-protein interactions in cells, such as with light (using light-oxygen-voltage-sensing domains) or cell-permeable small molecules by chemically induced dimerization.[62]

In a living cell, molecular motifs are embedded in a bigger network with upstream and downstream components. These components may alter the signaling capability of the modeling module. In the case of ultrasensitive modules, the sensitivity contribution of a module can differ from the sensitivity that the module sustains in isolation.

分子模体被嵌入到活细胞中一个更大的由上游或下游组件构成的网络中。这些组件可以改变建模模块的信令能力。在超灵敏模块的情况下,模块的灵敏度贡献可能不同于该模块在隔离状态下支持的灵敏度。


In a living cell, molecular motifs are embedded in a bigger network with upstream and downstream components. These components may alter the signaling capability of the modeling module. In the case of ultrasensitive modules, the sensitivity contribution of a module can differ from the sensitivity that the module sustains in isolation.[63][64]


Models inform the design of engineered biological systems by better predicting system behavior prior to fabrication. Synthetic biology benefits from better models of how biological molecules bind substrates and catalyze reactions, how DNA encodes the information needed to specify the cell and how multi-component integrated systems behave. Multiscale models of gene regulatory networks focus on synthetic biology applications. Simulations can model all biomolecular interactions in transcription, translation, regulation and induction of gene regulatory networks.

模型通过在制造之前更好地预测系统行为来指导工程生物系统的设计。合成生物学受益于更好的模型,这些模型包括生物分子如何结合底物和催化反应,DNA 如何编码指定细胞所需的信息,以及多组分综合系统如何运作。基因调控网络的多尺度模型聚焦于合成生物学的应用。模拟可以模拟所有生物分子间相互作用的转录,翻译,调节和基因调控网络的诱导。

Modeling 建模

Models inform the design of engineered biological systems by better predicting system behavior prior to fabrication. Synthetic biology benefits from better models of how biological molecules bind substrates and catalyze reactions, how DNA encodes the information needed to specify the cell and how multi-component integrated systems behave. Multiscale models of gene regulatory networks focus on synthetic biology applications. Simulations can model all biomolecular interactions in transcription, translation, regulation and induction of gene regulatory networks.[65]

[66]

[67]


Studies have considered the components of the DNA transcription mechanism. One desire of scientists creating synthetic biological circuits is to be able to control the transcription of synthetic DNA in unicellular organisms (prokaryotes) and in multicellular organisms (eukaryotes). One study tested the adjustability of synthetic transcription factors (sTFs) in areas of transcription output and cooperative ability among multiple transcription factor complexes. Researchers were able to mutate functional regions called zinc fingers, the DNA specific component of sTFs, to decrease their affinity for specific operator DNA sequence sites, and thus decrease the associated site-specific activity of the sTF (usually transcriptional regulation). They further used the zinc fingers as components of complex-forming sTFs, which are the eukaryotic translation mechanisms. and demonstrated both analog and digital computation in living cells. --袁一博讨论) “and demonstrated both analog and digital computation in living cells. ”这句首字母没有大写,不知是搬运时少了一点还是仅仅是格式错误。 They demonstrated that bacteria can be engineered to perform both analog and/or digital computation. In human cells research demonstrated a universal logic evaluator that operates in mammalian cells in 2007. Subsequently, researchers utilized this paradigm to demonstrate a proof-of-concept therapy that uses biological digital computation to detect and kill human cancer cells in 2011. Another group of researchers demonstrated in 2016 that principles of computer engineering, can be used to automate digital circuit design in bacterial cells. In 2017, researchers demonstrated the 'Boolean logic and arithmetic through DNA excision' (BLADE) system to engineer digital computation in human cells.

相关研究已经考虑到了 DNA 转录机制的组成部分。科学家创造合成生物电路,以期能够控制单细胞生物(原核生物)和多细胞生物(真核生物)中合成 DNA 的转录。一项研究测试了合成转录因子(sTFs)在转录输出和多个转录因子复合物之间的合作能力方面的可调节性。研究人员能够使被称为锌指——转录因子的一段特殊DNA——的功能区域突变,以减少它们对特定算子DNA 序列位点的亲和力,从而减少相关的特定位点的转录因子活性(通常是转录调控)。他们进一步使用锌指作为复杂地组成的转录因子的组成部分,这是真核翻译的机制。并在活细胞中进行了模拟和数字计算。他们证明了可以改造细菌使其同时执行模拟和/或数字计算。2007年,关于人类细胞的研究展示了一种在哺乳动物细胞中运作的通用逻辑求值器。随后,研究人员在2011年利用这一范式展示了一种概念验证疗法,利用生物数字计算来检测和杀死人类癌细胞。另一组研究人员在2016年证明了计算机工程的原理,可以用来自动化细菌细胞中的数字电路设计。2017年,研究人员演示了“通过 DNA 删除的布尔逻辑和算术”(BLADE)系统,用于在人类细胞中构建数字计算。

Synthetic transcription factors 合成转录因子

Studies have considered the components of the DNA transcription mechanism. One desire of scientists creating synthetic biological circuits is to be able to control the transcription of synthetic DNA in unicellular organisms (prokaryotes) and in multicellular organisms (eukaryotes). One study tested the adjustability of synthetic transcription factors (sTFs) in areas of transcription output and cooperative ability among multiple transcription factor complexes.[68] Researchers were able to mutate functional regions called zinc fingers, the DNA specific component of sTFs, to decrease their affinity for specific operator DNA sequence sites, and thus decrease the associated site-specific activity of the sTF (usually transcriptional regulation). They further used the zinc fingers as components of complex-forming sTFs, which are the eukaryotic translation mechanisms.[68]


A biosensor refers to an engineered organism, usually a bacterium, that is capable of reporting some ambient phenomenon such as the presence of heavy metals or toxins. One such system is the Lux operon of Aliivibrio fischeri, which codes for the enzyme that is the source of bacterial bioluminescence, and can be placed after a respondent promoter to express the luminescence genes in response to a specific environmental stimulus. One such sensor created, consisted of a bioluminescent bacterial coating on a photosensitive computer chip to detect certain petroleum pollutants. When the bacteria sense the pollutant, they luminesce. Another example of a similar mechanism is the detection of landmines by an engineered E.coli reporter strain capable of detecting TNT and its main degradation product DNT, and consequently producing a green fluorescent protein (GFP).

生物传感器是一种工用有机体,它能够报告周边某些环境现象,如重金属或毒素的存在,通常是细菌。其中一个这样的系统是 Aliivibrio 费氏弧菌的 Lux 操纵子,它编码的酶可以使细菌生物发光,可以放置在应答启动子之后表达发光基因以响应特定的环境刺激。其中一个传感器是由一个光敏计算机芯片上的生物发光细菌涂层组成的,用以检测某些石油污染物。当细菌感觉到污染物时,它们就会发光。另一个类似机制的例子是地雷的检测,用一个能够检测 TNT 及其主要降解产物 DNT 的大肠杆菌报告基因工程菌株,从而产生绿色荧光蛋白。

Applications 应用

Biological computers 生物计算机

Modified organisms can sense environmental signals and send output signals that can be detected and serve diagnostic purposes. Microbe cohorts have been used.

改良有机体可以感知环境信号,并发送能够被检测到的输出信号,用于诊断目的。微生物群落已经被应用于这种用途。

A biological computer refers to an engineered biological system that can perform computer-like operations, which is a dominant paradigm in synthetic biology. Researchers built and characterized a variety of logic gates in a number of organisms,[69] and demonstrated both analog and digital computation in living cells. They demonstrated that bacteria can be engineered to perform both analog and/or digital computation.[70][71] In human cells research demonstrated a universal logic evaluator that operates in mammalian cells in 2007.[72] Subsequently, researchers utilized this paradigm to demonstrate a proof-of-concept therapy that uses biological digital computation to detect and kill human cancer cells in 2011.[73] Another group of researchers demonstrated in 2016 that principles of computer engineering, can be used to automate digital circuit design in bacterial cells.[74] In 2017, researchers demonstrated the 'Boolean logic and arithmetic through DNA excision' (BLADE) system to engineer digital computation in human cells.[75]


Biosensors 生物传感器

Cells use interacting genes and proteins, which are called gene circuits, to implement diverse function, such as responding to environmental signals, decision making and communication. Three key components are involved: DNA, RNA and Synthetic biologist designed gene circuits that can control gene expression from several levels including transcriptional, post-transcriptional and translational levels.

细胞使用相互作用的基因和蛋白质,即所谓的基因回路,来实现不同的功能,如响应环境信号,决策和沟通。其中涉及到三个关键组成部分: DNA、 RNA 和合成生物学家设计的基因电路,可以从转录、转录后和翻译水平等几个层面控制基因表达。

A biosensor refers to an engineered organism, usually a bacterium, that is capable of reporting some ambient phenomenon such as the presence of heavy metals or toxins. One such system is the Lux operon of Aliivibrio fischeri,[76] which codes for the enzyme that is the source of bacterial bioluminescence, and can be placed after a respondent promoter to express the luminescence genes in response to a specific environmental stimulus.[77] One such sensor created, consisted of a bioluminescent bacterial coating on a photosensitive computer chip to detect certain petroleum pollutants. When the bacteria sense the pollutant, they luminesce.[78] Another example of a similar mechanism is the detection of landmines by an engineered E.coli reporter strain capable of detecting TNT and its main degradation product DNT, and consequently producing a green fluorescent protein (GFP).[79]


Traditional metabolic engineering has been bolstered by the introduction of combinations of foreign genes and optimization by directed evolution. This includes engineering E. coli and yeast for commercial production of a precursor of the antimalarial drug, Artemisinin.

通过引入外源基因的组合和定向进化,传统的代谢工程学得到巨大发展。这包括改造大肠杆菌和酵母菌,用于商业化生产抗疟药物青蒿素的前体。

Modified organisms can sense environmental signals and send output signals that can be detected and serve diagnostic purposes. Microbe cohorts have been used.[80]


Entire organisms have yet to be created from scratch, although living cells can be transformed with new DNA. --袁一博讨论)“Entire organisms have yet to be created from scratch, although living cells can be transformed with new DNA.”have 疑似应为 haven’t Several ways allow constructing synthetic DNA components and even entire synthetic genomes, but once the desired genetic code is obtained, it is integrated into a living cell that is expected to manifest the desired new capabilities or phenotypes while growing and thriving. Cell transformation is used to create biological circuits, which can be manipulated to yield desired outputs.

虽然活细胞可以通过新的 DNA 转化,但整个有机体还没有从头开始创造。有几种方法可以构建合成 DNA 组件,甚至是整个合成基因组,但是一旦获得了所需的遗传密码,它就会被整合到一个活细胞中,这个活细胞在生长和发育的过程中,有望表现所需的新能力或表型。细胞分化被用于创造生物电路,我们可以通过操纵这些电路来产生所需的输出。

Cell transformation 细胞分化

Cells use interacting genes and proteins, which are called gene circuits, to implement diverse function, such as responding to environmental signals, decision making and communication. Three key components are involved: DNA, RNA and Synthetic biologist designed gene circuits that can control gene expression from several levels including transcriptional, post-transcriptional and translational levels.


Traditional metabolic engineering has been bolstered by the introduction of combinations of foreign genes and optimization by directed evolution. This includes engineering E. coli and yeast for commercial production of a precursor of the antimalarial drug, Artemisinin.[81]

The Top7 protein was one of the first proteins designed for a fold that had never been seen before in nature

[[ Top7蛋白是最初为了折叠而设计的几个蛋白质之一,以前从未在自然界中见过]


Entire organisms have yet to be created from scratch, although living cells can be transformed with new DNA. Several ways allow constructing synthetic DNA components and even entire synthetic genomes, but once the desired genetic code is obtained, it is integrated into a living cell that is expected to manifest the desired new capabilities or phenotypes while growing and thriving.[82] Cell transformation is used to create biological circuits, which can be manipulated to yield desired outputs.[19][20]

Natural proteins can be engineered, for example, by directed evolution, novel protein structures that match or improve on the functionality of existing proteins can be produced. One group generated a helix bundle that was capable of binding oxygen with similar properties as hemoglobin, yet did not bind carbon monoxide. A similar protein structure was generated to support a variety of oxidoreductase activities while another formed a structurally and sequentially novel ATPase. Another group generated a family of G-protein coupled receptors that could be activated by the inert small molecule clozapine N-oxide but insensitive to the native ligand, acetylcholine; these receptors are known as DREADDs. Novel functionalities or protein specificity can also be engineered using computational approaches. One study was able to use two different computational methods – a bioinformatics and molecular modeling method to mine sequence databases, and a computational enzyme design method to reprogram enzyme specificity. Both methods resulted in designed enzymes with greater than 100 fold specificity for production of longer chain alcohols from sugar.

天然蛋白质可以被设计出来,例如,通过定向进化,新的蛋白质结构可以匹配或改进现有蛋白质的功能。其中一组可以产生能将血红蛋白与具有类似性质的氧结合的螺旋束,但不结合一氧化碳。一个类似的蛋白质结构被生成以支持多种氧化还原酶活性,而另一组生成一个在结构和顺序上全新的 ATP 酶。另一组产生了一类 g 蛋白偶联受体,这类受体可以被惰性小分子N-氧化氯氮平激活,但对天然配体乙酰胆碱不敏感; 这些受体被称为 DREADDs。新的功能或蛋白质特异性也可以利用计算方法进行设计。一项研究能够使用两种不同的计算方法——生物信息学和分子模拟方法挖掘序列数据库,使用计算酶设计方法重新编写酶的专一性。这两种方法都可以使设计的酶具有大于100倍的专一性,可以用糖生产出长链醇。


By integrating synthetic biology with materials science, it would be possible to use cells as microscopic molecular foundries to produce materials with properties whose properties were genetically encoded. Re-engineering has produced Curli fibers, the amyloid component of extracellular material of biofilms, as a platform for programmable nanomaterial. These nanofibers were genetically constructed for specific functions, including adhesion to substrates, nanoparticle templating and protein immobilization.[83]

Another common investigation is expansion of the natural set of 20 amino acids. Excluding stop codons, 61 codons have been identified, but only 20 amino acids are coded generally in all organisms. Certain codons are engineered to code for alternative amino acids including: nonstandard amino acids such as O-methyl tyrosine; or exogenous amino acids such as 4-fluorophenylalanine. Typically, these projects make use of re-coded nonsense suppressor tRNA-Aminoacyl tRNA synthetase pairs from other organisms, though in most cases substantial engineering is required.

另一个常见的研究是对20种天然氨基酸的扩展。除了终止密码子, 61个密码子已被破译出,但所有生物体中一般只有20个氨基酸。某些密码子被设计为编码可替代的氨基酸,包括: 非标准氨基酸,如 o- 甲基酪氨酸; 或外源氨基酸,如4- 氟苯丙氨酸。通常情况下,这些项目利用从其他生物体获取的重新编码的无意义抑制 tRNA-氨酰基 tRNA 合成酶对,虽然在大多数情况下这需要大量的工程。


Designed proteins 设计蛋白质

Other researchers investigated protein structure and function by reducing the normal set of 20 amino acids. Limited protein sequence libraries are made by generating proteins where groups of amino acids may be replaced by a single amino acid. For instance, several non-polar amino acids within a protein can all be replaced with a single non-polar amino acid. . One project demonstrated that an engineered version of Chorismate mutase still had catalytic activity when only 9 amino acids were used.

其他研究人员通过减少一般的20种天然氨基酸来研究蛋白质的结构和功能。有限的蛋白质序列库是通过生成蛋白质制成的,其中一组氨基酸可以被一个单一的氨基酸所取代。例如,一个蛋白质中的几个非极性氨基酸都可以被一个非极性氨基酸所取代。.一个研究项目证明了,当只使用9种氨基酸时,一种改造过的分支酸变位酶仍然具有催化活性。


文件:Top7.png
The Top7 protein was one of the first proteins designed for a fold that had never been seen before in nature[84]

Researchers and companies practice synthetic biology to synthesize industrial enzymes with high activity, optimal yields and effectiveness. These synthesized enzymes aim to improve products such as detergents and lactose-free dairy products, as well as make them more cost effective. The improvements of metabolic engineering by synthetic biology is an example of a biotechnological technique utilized in industry to discover pharmaceuticals and fermentive chemicals. Synthetic biology may investigate modular pathway systems in biochemical production and increase yields of metabolic production. Artificial enzymatic activity and subsequent effects on metabolic reaction rates and yields may develop "efficient new strategies for improving cellular properties ... for industrially important biochemical production".

研究人员和公司运用合成生物学来合成具有高活性、最佳产量和有效性的工业酶。这些合成酶旨在改善产品,如洗涤剂和无乳糖乳制品,以及使他们更具成本效益。合成生物学对代谢工程学的改进是生物技术用于工业发现药物和发酵性化学品的一个典例。合成生物学可以研究生化生产中的模块化途径系统,并提高代谢生产的产量。人工酶活性及其对代谢反应速率和产量的后续影响可能推动“改善细胞特性有效的新策略...... 用于重要的工业生化产品”。


Natural proteins can be engineered, for example, by directed evolution, novel protein structures that match or improve on the functionality of existing proteins can be produced. One group generated a helix bundle that was capable of binding oxygen with similar properties as hemoglobin, yet did not bind carbon monoxide.[85] A similar protein structure was generated to support a variety of oxidoreductase activities [86] while another formed a structurally and sequentially novel ATPase.[87] Another group generated a family of G-protein coupled receptors that could be activated by the inert small molecule clozapine N-oxide but insensitive to the native ligand, acetylcholine; these receptors are known as DREADDs.[88] Novel functionalities or protein specificity can also be engineered using computational approaches. One study was able to use two different computational methods – a bioinformatics and molecular modeling method to mine sequence databases, and a computational enzyme design method to reprogram enzyme specificity. Both methods resulted in designed enzymes with greater than 100 fold specificity for production of longer chain alcohols from sugar.[89]


Scientists can encode digital information onto a single strand of synthetic DNA. In 2012, George M. Church encoded one of his books about synthetic biology in DNA. The 5.3 Mb of data was more than 1000 times greater than the previous largest amount of information to be stored in synthesized DNA. A similar project encoded the complete sonnets of William Shakespeare in DNA. More generally, algorithms such as NUPACK, ViennaRNA, Ribosome Binding Site Calculator, Cello, and Non-Repetitive Parts Calculator enables the design of new genetic systems.

科学家可以将数字信息编码到一条合成 DNA 链上。2012年,乔治·M·丘奇用 DNA 将他的一本关于合成生物学的书编码。这5.3 Mb 的数据量比之前存储在合成 DNA 中的最大信息量大了1000多倍。一个类似的项目将威廉·莎士比亚的十四行诗全部编码在 DNA 中。更广泛地说,例如努派克,维也纳,核糖体结合位点算子,大提琴,和非重复部分算子等算法使新遗传系统的设计成为可能。

Another common investigation is expansion of the natural set of 20 amino acids. Excluding stop codons, 61 codons have been identified, but only 20 amino acids are coded generally in all organisms. Certain codons are engineered to code for alternative amino acids including: nonstandard amino acids such as O-methyl tyrosine; or exogenous amino acids such as 4-fluorophenylalanine. Typically, these projects make use of re-coded nonsense suppressor tRNA-Aminoacyl tRNA synthetase pairs from other organisms, though in most cases substantial engineering is required.[90]


Many technologies have been developed for incorporating unnatural nucleotides and amino acids into nucleic acids and proteins, both in vitro and in vivo. For example, in May 2014, researchers announced that they had successfully introduced two new artificial nucleotides into bacterial DNA. By including individual artificial nucleotides in the culture media, they were able to exchange the bacteria 24 times; they did not generate mRNA or proteins able to use the artificial nucleotides.

无论是在体外还是体内,在核酸和蛋白质中将非天然的核苷酸和氨基酸结合的技术已经实现。例如,2014年5月,研究人员宣布他们已经成功地将两种新的人工核苷酸引入细菌 DNA。通过在培养基中加入单个的人工核苷酸,他们能够交换细菌24次; 但是他们没有得到人工核苷酸表达的 mRNA 或蛋白质。

Other researchers investigated protein structure and function by reducing the normal set of 20 amino acids. Limited protein sequence libraries are made by generating proteins where groups of amino acids may be replaced by a single amino acid.[91] For instance, several non-polar amino acids within a protein can all be replaced with a single non-polar amino acid.[92] . One project demonstrated that an engineered version of Chorismate mutase still had catalytic activity when only 9 amino acids were used.[93]


Researchers and companies practice synthetic biology to synthesize industrial enzymes with high activity, optimal yields and effectiveness. These synthesized enzymes aim to improve products such as detergents and lactose-free dairy products, as well as make them more cost effective.[94] The improvements of metabolic engineering by synthetic biology is an example of a biotechnological technique utilized in industry to discover pharmaceuticals and fermentive chemicals. Synthetic biology may investigate modular pathway systems in biochemical production and increase yields of metabolic production. Artificial enzymatic activity and subsequent effects on metabolic reaction rates and yields may develop "efficient new strategies for improving cellular properties ... for industrially important biochemical production".[95]

Synthetic biology raised NASA's interest as it could help to produce resources for astronauts from a restricted portfolio of compounds sent from Earth. On Mars, in particular, synthetic biology could lead to production processes based on local resources, making it a powerful tool in the development of manned outposts with less dependence on Earth.

合成生物学引起了美国国家航空航天局的兴趣,因为它可以促使来自地球的受限化合物组合为宇航员生产资源。特别是在火星上,合成生物学可以产生基于局部资源的生产过程,使其成为开发对地球依赖性较低的载人前哨站的有力工具。


Designed nucleic acid systems 设计核酸系统

Scientists can encode digital information onto a single strand of synthetic DNA. In 2012, George M. Church encoded one of his books about synthetic biology in DNA. The 5.3 Mb of data was more than 1000 times greater than the previous largest amount of information to be stored in synthesized DNA.[96] A similar project encoded the complete sonnets of William Shakespeare in DNA.[97] More generally, algorithms such as NUPACK,[98] ViennaRNA,[99] Ribosome Binding Site Calculator,[100] Cello,[101] and Non-Repetitive Parts Calculator[102] enables the design of new genetic systems.


Gene functions in the minimal genome of the synthetic organism, Syn 3.

在合成生物的最小基因组中发挥功能的基因,Syn 3.

Many technologies have been developed for incorporating unnatural nucleotides and amino acids into nucleic acids and proteins, both in vitro and in vivo. For example, in May 2014, researchers announced that they had successfully introduced two new artificial nucleotides into bacterial DNA. By including individual artificial nucleotides in the culture media, they were able to exchange the bacteria 24 times; they did not generate mRNA or proteins able to use the artificial nucleotides.[103][104][105]

One important topic in synthetic biology is synthetic life, that is concerned with hypothetical organisms created in vitro from biomolecules and/or chemical analogues thereof. Synthetic life experiments attempt to either probe the origins of life, study some of the properties of life, or more ambitiously to recreate life from non-living (abiotic) components. Synthetic life biology attempts to create living organisms capable of carrying out important functions, from manufacturing pharmaceuticals to detoxifying polluted land and water. In medicine, it offers prospects of using designer biological parts as a starting point for new classes of therapies and diagnostic tools. Nobody has been able to create such a cell. The host cells were able to grow and replicate. The Mycoplasma laboratorium is the only living organism with completely engineered genome.

合成生物学的一个重要课题是合成生命,它涉及到在体外由生物分子和/或其化学类似物创造的假想生物体。合成生命实验或者试图探索生命的起源,研究生命的某些特性,或者更雄心勃勃地,试图从非生命(非生物)组成部分中重新创造生命。合成生命生物学试图创造能够执行重要功能的生命有机体,从制造药品到净化被污染的土地和水。在医学上,它提供了使用设计生物学部件作为新类型治疗和诊断工具的起点的前景。没有人能够制造出这样的细胞。宿主细胞能够生长和复制。实验室合成支原体是唯一拥有完全工程化基因组的生物体。


Space exploration 太空探索

The first living organism with 'artificial' expanded DNA code was presented in 2014; the team used E. coli that had its genome extracted and replaced with a chromosome with an expanded genetic code. The nucleosides added are d5SICS and dNaM. followed by national synthetic cell organizations in several countries, including FabriCell, MaxSynBio and BaSyC. --袁一博讨论)“followed by national synthetic cell organizations in several countries, including FabriCell, MaxSynBio and BaSyC.”该句首字母未大写,疑似搬运时少了部分语句。 The European synthetic cell efforts were unified in 2019 as SynCellEU initiative.

2014年,第一个具有人工扩展 DNA 编码的有机活体问世; 研究小组使用大肠杆菌提取了它的基因组,并用扩展基因编码的染色体替换了它。添加的核苷是 d5SICS 和 dNaM。其次是一些国家的国家合成细胞组织,包括 FabriCell,MaxSynBio 和 BaSyC。SynCellEU 倡议在2019年总结了欧洲合成细胞的相关工作。

Synthetic biology raised NASA's interest as it could help to produce resources for astronauts from a restricted portfolio of compounds sent from Earth.[106][107][108] On Mars, in particular, synthetic biology could lead to production processes based on local resources, making it a powerful tool in the development of manned outposts with less dependence on Earth.[106] Work has gone into developing plant strains that are able to cope with the harsh Martian environment, using similar techniques to those employed to increase resilience to certain environmental factors in agricultural crops.[109]


Synthetic life 合成生命

模板:Further

Bacteria have long been used in cancer treatment. Bifidobacterium and Clostridium selectively colonize tumors and reduce their size. Recently synthetic biologists reprogrammed bacteria to sense and respond to a particular cancer state. Most often bacteria are used to deliver a therapeutic molecule directly to the tumor to minimize off-target effects. To target the tumor cells, peptides that can specifically recognize a tumor were expressed on the surfaces of bacteria. Peptides used include an affibody molecule that specifically targets human epidermal growth factor receptor 2 and a synthetic adhesin. The other way is to allow bacteria to sense the tumor microenvironment, for example hypoxia, by building an AND logic gate into bacteria. The bacteria then only release target therapeutic molecules to the tumor through either lysis or the bacterial secretion system. Lysis has the advantage that it can stimulate the immune system and control growth. Multiple types of secretion systems can be used and other strategies as well. The system is inducible by external signals. Inducers include chemicals, electromagnetic or light waves.

长期以来,细菌一直被用于癌症治疗。双歧杆菌和梭状芽胞杆菌选择性地定殖于肿瘤并减小肿瘤体积。最近,合成生物学家对细菌进行了重新编码,使其能够感知特定的癌症状态并对其做出反应。大多数情况下,细菌被用来直接向肿瘤输送治疗分子,以最小化脱靶效应。为了定靶于肿瘤细胞,细菌表面表达出了可以特异性识别肿瘤的肽。识别过程中涉及的多肽包括一个特定作用于人类表皮生长因子受体的粘附分子和一个合成粘附素。另一种方法是通过在细菌中建立一个与逻辑门让细菌感知肿瘤的微环境,例如,缺氧。然后,细菌只通过溶菌或细菌分泌系统向肿瘤释放靶向治疗分子。溶菌具有刺激免疫系统和控制生长的优点。这个过程中可以使用多种类型的分泌系统和其他策略。该系统由外部信号诱导。这些诱导因子包括化学物质、电磁波或光波。

文件:Syn3 genome.svg
Gene functions in the minimal genome of the synthetic organism, Syn 3.[110]

One important topic in synthetic biology is synthetic life, that is concerned with hypothetical organisms created in vitro from biomolecules and/or chemical analogues thereof. Synthetic life experiments attempt to either probe the origins of life, study some of the properties of life, or more ambitiously to recreate life from non-living (abiotic) components. Synthetic life biology attempts to create living organisms capable of carrying out important functions, from manufacturing pharmaceuticals to detoxifying polluted land and water.[111] In medicine, it offers prospects of using designer biological parts as a starting point for new classes of therapies and diagnostic tools.[111]

Multiple species and strains are applied in these therapeutics. Most commonly used bacteria are Salmonella typhimurium, Escherichia Coli, Bifidobacteria, Streptococcus, Lactobacillus, Listeria and Bacillus subtilis. Each of these species have their own property and are unique to cancer therapy in terms of tissue colonization, interaction with immune system and ease of application.

在这些治疗方法中应用了多种菌株。最常用的细菌是鼠伤寒沙门氏菌、大肠桿菌、双歧杆菌、链球菌、乳酸菌、李斯特菌和枯草杆菌。这些物种中的每一个都有自己的特性。在定殖组织、与免疫系统的相互作用和易于应用方面,它们对癌症治疗各有独到之处。


A living "artificial cell" has been defined as a completely synthetic cell that can capture energy, maintain ion gradients, contain macromolecules as well as store information and have the ability to mutate.[112] Nobody has been able to create such a cell.[112]


The immune system plays an important role in cancer and can be harnessed to attack cancer cells. Cell-based therapies focus on immunotherapies, mostly by engineering T cells.

免疫系统在癌症中起着重要作用。可以利用免疫系统攻击癌细胞。以细胞为基础的疗法主要是免疫疗法,主要方法是通过改造 T 细胞来完成治疗。

A completely synthetic bacterial chromosome was produced in 2010 by Craig Venter, and his team introduced it to genomically emptied bacterial host cells.[26] The host cells were able to grow and replicate.[113][114] The Mycoplasma laboratorium is the only living organism with completely engineered genome.


T cell receptors were engineered and ‘trained’ to detect cancer epitopes. Chimeric antigen receptors (CARs) are composed of a fragment of an antibody fused to intracellular T cell signaling domains that can activate and trigger proliferation of the cell. A second generation CAR-based therapy was approved by FDA.

T 细胞受体被设计和“训练”用以检测癌症表位。嵌合抗原受体(CAR)是由融合于细胞内 T 细胞信号域的抗体片段组成,这些信号域可以激活并触发细胞增殖。美国食品药品监督管理局(FDA)批准了第二代基于嵌合抗原受体的基因治疗。

The first living organism with 'artificial' expanded DNA code was presented in 2014; the team used E. coli that had its genome extracted and replaced with a chromosome with an expanded genetic code. The nucleosides added are d5SICS and dNaM.[105]


Gene switches were designed to enhance safety of the treatment. Kill switches were developed to terminate the therapy should the patient show severe side effects. Mechanisms can more finely control the system and stop and reactivate it. Since the number of T-cells are important for therapy persistence and severity, growth of T-cells is also controlled to dial the effectiveness and safety of therapeutics.

基因开关的设计初衷是提高治疗的安全性。如果病人出现严重的副作用,杀伤开关就会终止治疗。这种机制可以更好地控制系统,停止和重新激活它。由于 T 细胞的数量对治疗的持续性和强度非常重要,因此 T 细胞的生长也受到控制,从而平衡治疗的有效性和安全性。

In May 2019, researchers, in a milestone effort, reported the creation of a new synthetic (possibly artificial) form of viable life, a variant of the bacteria Escherichia coli, by reducing the natural number of 64 codons in the bacterial genome to 59 codons instead, in order to encode 20 amino acids.[32][33]


Although several mechanisms can improve safety and control, limitations include the difficulty of inducing large DNA circuits into the cells and risks associated with introducing foreign components, especially proteins, into cells.

虽然有几种机制可以提高安全性和控制性,但他们也都存在局限性,包括很难将大型 DNA 电路诱导入细胞,以及将外来成分,特别是蛋白质引入细胞的风险。

In 2017 the international Build-a-Cell large-scale research collaboration for the construction of synthetic living cell was started,[115] followed by national synthetic cell organizations in several countries, including FabriCell,[116] MaxSynBio[117] and BaSyC.[118] The European synthetic cell efforts were unified in 2019 as SynCellEU initiative.[119]


Drug delivery platforms 药物输送平台

Engineered bacteria-based platform 基于细菌设计的平台

Bacteria have long been used in cancer treatment. Bifidobacterium and Clostridium selectively colonize tumors and reduce their size.[120] Recently synthetic biologists reprogrammed bacteria to sense and respond to a particular cancer state. Most often bacteria are used to deliver a therapeutic molecule directly to the tumor to minimize off-target effects. To target the tumor cells, peptides that can specifically recognize a tumor were expressed on the surfaces of bacteria. Peptides used include an affibody molecule that specifically targets human epidermal growth factor receptor 2[121] and a synthetic adhesin.[122] The other way is to allow bacteria to sense the tumor microenvironment, for example hypoxia, by building an AND logic gate into bacteria.[123] The bacteria then only release target therapeutic molecules to the tumor through either lysis[124] or the bacterial secretion system.[125] Lysis has the advantage that it can stimulate the immune system and control growth. Multiple types of secretion systems can be used and other strategies as well. The system is inducible by external signals. Inducers include chemicals, electromagnetic or light waves.

The creation of new life and the tampering of existing life has raised ethical concerns in the field of synthetic biology and are actively being discussed.

创造新生命以及篡改现有生命引起了合成生物学领域的伦理问题,目前正处于积极的讨论中。


Multiple species and strains are applied in these therapeutics. Most commonly used bacteria are Salmonella typhimurium, Escherichia Coli, Bifidobacteria, Streptococcus, Lactobacillus, Listeria and Bacillus subtilis. Each of these species have their own property and are unique to cancer therapy in terms of tissue colonization, interaction with immune system and ease of application.


The ethical aspects of synthetic biology has 3 main features: biosafety, biosecurity, and the creation of new life forms. Other ethical issues mentioned include the regulation of new creations, patent management of new creations, benefit distribution, and research integrity.

合成生物学的伦理方面有三个主要特点: 生物研究安全性、生物安全性和创造新的生命形式。其他提到的伦理问题包括新生命的管理、新生命的专利管理、利益分配和研究的完整性。

Cell-based platform 基于细胞的平台

The immune system plays an important role in cancer and can be harnessed to attack cancer cells. Cell-based therapies focus on immunotherapies, mostly by engineering T cells.

Ethical issues have surfaced for recombinant DNA and genetically modified organism (GMO) technologies and extensive regulations of genetic engineering and pathogen research were in place in many jurisdictions. Amy Gutmann, former head of the Presidential Bioethics Commission, argued that we should avoid the temptation to over-regulate synthetic biology in general, and genetic engineering in particular. According to Gutmann, "Regulatory parsimony is especially important in emerging technologies...where the temptation to stifle innovation on the basis of uncertainty and fear of the unknown is particularly great. The blunt instruments of statutory and regulatory restraint may not only inhibit the distribution of new benefits, but can be counterproductive to security and safety by preventing researchers from developing effective safeguards.".

重组 DNA 和转基因生物(GMO)技术的伦理问题已经浮出水面,许多司法管辖区对基因工程和病原体研究有着广泛的规定。生物伦理总统委员会前任主席艾米 · 古特曼认为,我们应该避免过度监管合成生物学,尤其是基因工程。古特曼认为,“过度监管在新兴技术领域尤为显要...... 在这些领域,处于不确定性和对未知事物的恐惧而扼杀创新的倾向尤为强烈。法律和监管限制的生硬手段可能不仅会抑制新利益的分配,而且可能阻碍研究人员制定有效的保障措施,从而对研究安全性和生命安全性产生反作用。".


T cell receptors were engineered and ‘trained’ to detect cancer epitopes. Chimeric antigen receptors (CARs) are composed of a fragment of an antibody fused to intracellular T cell signaling domains that can activate and trigger proliferation of the cell. A second generation CAR-based therapy was approved by FDA.[citation needed]


Gene switches were designed to enhance safety of the treatment. Kill switches were developed to terminate the therapy should the patient show severe side effects.[126] Mechanisms can more finely control the system and stop and reactivate it.[127][128] Since the number of T-cells are important for therapy persistence and severity, growth of T-cells is also controlled to dial the effectiveness and safety of therapeutics.[129]

One ethical question is whether or not it is acceptable to create new life forms, sometimes known as "playing God". Currently, the creation of new life forms not present in nature is at small-scale, the potential benefits and dangers remain unknown, and careful consideration and oversight are ensured for most studies. Regarding auxotrophy, bacteria and yeast can be engineered to be unable to produce histidine, an important amino acid for all life. Such organisms can thus only be grown on histidine-rich media in laboratory conditions, nullifying fears that they could spread into undesirable areas.

有这样一个道德问题,创造新的生命形式,或称“扮演上帝”,是否可以接受。目前,自然界中不存在的新生命形式的创造规模很小,潜在的好处和风险仍然不为人知,并且大多数研究确保进行了认真的考虑和监督。通过制造营养缺陷,细菌和酵母可以被改造为不能生产组氨酸的类型。组氨酸是一种对所有生命来说都很重要的氨基酸。因此,这些微生物只能在实验室条件下在富含组氨酸的培养基上生长,从而消除了人们对它们可能扩散到不良区域的担忧。



Ethics 伦理问题

Some ethical issues relate to biosecurity, where biosynthetic technologies could be deliberately used to cause harm to society and/or the environment. Since synthetic biology raises ethical issues and biosecurity issues, humanity must consider and plan on how to deal with potentially harmful creations, and what kinds of ethical measures could possibly be employed to deter nefarious biosynthetic technologies. With the exception of regulating synthetic biology and biotechnology companies, however, the issues are not seen as new because they were raised during the earlier recombinant DNA and genetically modified organism (GMO) debates and extensive regulations of genetic engineering and pathogen research are already in place in many jurisdictions.

一些伦理问题与生物安全有关,在这方面,生物合成技术可能被有意用以破坏社会和/或环境。由于合成生物学引起了伦理问题和生物安全问题,人类必须考虑和计划如何处理潜在的有害创造物,以及何种伦理措施具有阻止邪恶的生物合成技术的可行性。然而,除了监管合成生物学和生物技术公司之外,这些问题并不被视为新问题,因为它们是在早期的重组 DNA 和转基因生物(GMO)辩论中提出的,而且许多司法辖区已经对基因工程和病原体研究进行了广泛的监管。< br/>

模板:Update


The creation of new life and the tampering of existing life has raised ethical concerns in the field of synthetic biology and are actively being discussed.[130]


The European Union-funded project SYNBIOSAFE has issued reports on how to manage synthetic biology. A 2007 paper identified key issues in safety, security, ethics and the science-society interface, which the project defined as public education and ongoing dialogue among scientists, businesses, government and ethicists. The key security issues that SYNBIOSAFE identified involved engaging companies that sell synthetic DNA and the biohacking community of amateur biologists. Key ethical issues concerned the creation of new life forms.

欧盟资助的项目 SYNBIOSAFE 已经发布了关于如何管理合成生物学的报告。2007年的一篇论文确定了技术安全、生命安全、伦理和科学-社会接口方面的关键问题,并将其定义为公共教育和科学家、企业、政府和伦理学家之间的持续交流。SYNBIOSAFE 确定的关键生命安全问题涉及到销售合成 DNA 的公司和业余生物学家组成的生物黑客社区。关键的伦理问题涉及到创造新的生命形式。

Common ethical questions include: 常见的伦理问题包括:


A subsequent report focused on biosecurity, especially the so-called dual-use challenge. For example, while synthetic biology may lead to more efficient production of medical treatments, it may also lead to synthesis or modification of harmful pathogens (e.g., smallpox). The biohacking community remains a source of special concern, as the distributed and diffuse nature of open-source biotechnology makes it difficult to track, regulate or mitigate potential concerns over biosafety and biosecurity.

随后的一份聚焦于于生物安全的报告,特别是所谓的两用挑战。例如,虽然合成生物学可能带来更有效的医疗生产,但它也可能合成或改造出有害的病原体(例如天花)。生物黑客仍然是一个特别令人关切的问题,因为开源生物技术的分布和扩散性质使得跟踪、管理或减轻对生物安全和生物安保的隐忧变得困难。

  • Is it morally right to tamper with nature?

篡改自然在道德上是正确的吗?

  • Is one playing God when creating new life?

创造新生命时,人是否就是上帝?

COSY, another European initiative, focuses on public perception and communication. To better communicate synthetic biology and its societal ramifications to a broader public, COSY and SYNBIOSAFE published SYNBIOSAFE, a 38-minute documentary film, in October 2009.

COSY 是欧洲的另一项倡议,主要关注于公众认知和交流。为了更好地向更广泛的公众宣传合成生物学及其社会影响,COSY 和 SYNBIOSAFE 于2009年10月出版了一部38分钟的纪录片《安全的合成生物学》。

  • What happens if a synthetic organism accidentally escapes?

如果一种合成生命体意外地从实验室中泄露出去,会发生什么?

  • What if an individual misuses synthetic biology and creates a harmful entity (e.g., a biological weapon)?

假如某个个体错误地使用合成生物学并制造了一个有害的实体,那该怎么办?

The International Association Synthetic Biology has proposed self-regulation. This proposes specific measures that the synthetic biology industry, especially DNA synthesis companies, should implement. In 2007, a group led by scientists from leading DNA-synthesis companies published a "practical plan for developing an effective oversight framework for the DNA-synthesis industry".

国际合成生物学协会已经建议进行自我调节。它提出了合成生物产业,特别是 DNA 合成公司,应该实施的具体措施。2007年,由主要的 DNA 合成公司的科学家领导的一个小组发表了“为 DNA 合成工业制定有效监督框架的实用计划”。

  • Who will have control of and access to the products of synthetic biology?

谁会拥有控制和访问合成生物产品的权限?

  • Who will gain from these innovations? Investors? Medical patients? Industrial farmers?

谁会从这些创新中获利?投资者?患者?工业农民?

On July 9–10, 2009, the National Academies' Committee of Science, Technology & Law convened a symposium on "Opportunities and Challenges in the Emerging Field of Synthetic Biology".

2009年7月9日至10日,美国国家学院科学、技术和法律委员会召开了一次名为“合成生物学新兴领域的机遇与挑战”的研讨会。

  • Does the patent system allow patents on living organisms? What about parts of organisms, like HIV resistance genes in humans?[131]
  • What if a new creation is deserving of moral or legal status?

如果一个新生命理应拥有道德和法律地位该怎么办?

After the publication of the first synthetic genome and the accompanying media coverage about "life" being created, President Barack Obama established the Presidential Commission for the Study of Bioethical Issues to study synthetic biology. The commission convened a series of meetings, and issued a report in December 2010 titled "New Directions: The Ethics of Synthetic Biology and Emerging Technologies." The commission stated that "while Venter’s achievement marked a significant technical advance in demonstrating that a relatively large genome could be accurately synthesized and substituted for another, it did not amount to the “creation of life”. It noted that synthetic biology is an emerging field, which creates potential risks and rewards. The commission did not recommend policy or oversight changes and called for continued funding of the research and new funding for monitoring, study of emerging ethical issues and public education. These security issues may be avoided by regulating industry uses of biotechnology through policy legislation. Federal guidelines on genetic manipulation are being proposed by "the President's Bioethics Commission ... in response to the announced creation of a self-replicating cell from a chemically synthesized genome, put forward 18 recommendations not only for regulating the science ... for educating the public". Richard Lewontin wrote that some of the safety tenets for oversight discussed in The Principles for the Oversight of Synthetic Biology are reasonable, but that the main problem with the recommendations in the manifesto is that "the public at large lacks the ability to enforce any meaningful realization of those recommendations".

在发表了第一个合成基因组以及随之而来的关于”生命”的媒体报道之后,巴拉克·奥巴马总统设立了研究合成生物学的生物伦理问题总统委员会。该委员会召开了一系列会议,并于2010年12月发布了一份题为《新方向: 合成生物学和新兴技术的伦理学》的报告。委员会指出:“虽然文特尔的成就标志着一项重大的技术进步,证明了一个相对较大的基因组可以准确地合成和替代另一个基因组,但它并不等于‘创造生命’。”报告指出,合成生物学是一个新兴的领域,它产生了潜在的风险和回报。该委员会没有对政策或监督方面的改变提出建议,并呼吁继续为研究提供资金,并为监测、研究新出现的道德问题和公共教育提供新资金。这些安全问题可以通过政策立法规范生物技术的工业用途来避免。“生物伦理总统委员会正在提出关于基因操纵的联邦指导方针...... 作为对宣布从化学合成的基因组中创造出自我复制细胞的回应,提出了18项建议,不仅仅是为了规范科学...... 为了教育公众。”。理查德·路文汀 (Richard Lewontin) 写道,《合成生物学监督原则》中讨论的一些监督安全原则是合理的,但宣言中的建议存在的主要问题是“广大公众缺乏能力,无法强制任意有意义地实现这些建议”。


The ethical aspects of synthetic biology has 3 main features: biosafety, biosecurity, and the creation of new life forms.[132] Other ethical issues mentioned include the regulation of new creations, patent management of new creations, benefit distribution, and research integrity.[133][130]


Ethical issues have surfaced for recombinant DNA and genetically modified organism (GMO) technologies and extensive regulations of genetic engineering and pathogen research were in place in many jurisdictions. Amy Gutmann, former head of the Presidential Bioethics Commission, argued that we should avoid the temptation to over-regulate synthetic biology in general, and genetic engineering in particular. According to Gutmann, "Regulatory parsimony is especially important in emerging technologies...where the temptation to stifle innovation on the basis of uncertainty and fear of the unknown is particularly great. The blunt instruments of statutory and regulatory restraint may not only inhibit the distribution of new benefits, but can be counterproductive to security and safety by preventing researchers from developing effective safeguards.".[134]


The hazards of synthetic biology include biosafety hazards to workers and the public, biosecurity hazards stemming from deliberate engineering of organisms to cause harm, and environmental hazards. The biosafety hazards are similar to those for existing fields of biotechnology, mainly exposure to pathogens and toxic chemicals, although novel synthetic organisms may have novel risks. For biosecurity, there is concern that synthetic or redesigned organisms could theoretically be used for bioterrorism. Potential risks include recreating known pathogens from scratch, engineering existing pathogens to be more dangerous, and engineering microbes to produce harmful biochemicals. Lastly, environmental hazards include adverse effects on biodiversity and ecosystem services, including potential changes to land use resulting from agricultural use of synthetic organisms.

合成生物学的危害包括对工人和公众的生物安全危害、蓄意设计可造成危害的生物体所产生的生物安全危害以及环境危害。生物安全危害类似于现有生物技术领域的危害,尽管新的合成生物可能有新的风险,它的主要形式是接触病原体和有毒化学品。为了生物安全,人们担心人工合成或重新设计的生物体在理论上可能被用于生物恐怖主义。潜在的风险包括从零开始再造已知的病原体,将现有的病原体设计成更危险的,以及设计微生物来生产有害的生物化学产品。最后,环境危害包括合成生物学对生物多样性和生态系统服务的不利影响,包括在农业上利用合成生物体对土地使用的潜在变化。

The "creation" of life 创造生命

Existing risk analysis systems for GMOs are generally considered sufficient for synthetic organisms, although there may be difficulties for an organism built "bottom-up" from individual genetic sequences. Synthetic biology generally falls under existing regulations for GMOs and biotechnology in general, and any regulations that exist for downstream commercial products, although there are generally no regulations in any jurisdiction that are specific to synthetic biology.

通常认为,尽管由单个基因序列构建”自下而上”的生物体可能存在困难,现有的转基因生物风险分析系统足以用于合成生物体。一般而言,尽管任何法域都没有专门针对合成生物学的条例,合成生物学属于现有的转基因生物和生物技术条例的范围,也属于现有的关于下游商业产品的条例的范围。

One ethical question is whether or not it is acceptable to create new life forms, sometimes known as "playing God". Currently, the creation of new life forms not present in nature is at small-scale, the potential benefits and dangers remain unknown, and careful consideration and oversight are ensured for most studies.[130] Many advocates express the great potential value—to agriculture, medicine, and academic knowledge, among other fields—of creating artificial life forms. Creation of new entities could expand scientific knowledge well beyond what is currently known from studying natural phenomena. Yet there is concern that artificial life forms may reduce nature’s "purity" (i.e., nature could be somehow corrupted by human intervention and manipulation) and potentially influence the adoption of more engineering-like principles instead of biodiversity- and nature-focused ideals. Some are also concerned that if an artificial life form were to be released into nature, it could hamper biodiversity by beating out natural species for resources (similar to how algal blooms kill marine species). Another concern involves the ethical treatment of newly created entities if they happen to sense pain, sentience, and self-perception. Should such life be given moral or legal rights? If so, how?


Biosafety and biocontainment 生物技术安全和生物抑制

What is most ethically appropriate when considering biosafety measures? How can accidental introduction of synthetic life in the natural environment be avoided? Much ethical consideration and critical thought has been given to these questions. Biosafety not only refers to biological containment; it also refers to strides taken to protect the public from potentially hazardous biological agents. Even though such concerns are important and remain unanswered, not all products of synthetic biology present concern for biological safety or negative consequences for the environment. It is argued that most synthetic technologies are benign and are incapable of flourishing in the outside world due to their "unnatural" characteristics as there is yet to be an example of a transgenic microbe conferred with a fitness advantage in the wild.


In general, existing hazard controls, risk assessment methodologies, and regulations developed for traditional genetically modified organisms (GMOs) are considered to be sufficient for synthetic organisms. "Extrinsic" biocontainment methods in a laboratory context include physical containment through biosafety cabinets and gloveboxes, as well as personal protective equipment. In an agricultural context they include isolation distances and pollen barriers, similar to methods for biocontainment of GMOs. Synthetic organisms may offer increased hazard control because they can be engineered with "intrinsic" biocontainment methods that limit their growth in an uncontained environment, or prevent horizontal gene transfer to natural organisms. Examples of intrinsic biocontainment include auxotrophy, biological kill switches, inability of the organism to replicate or to pass modified or synthetic genes to offspring, and the use of xenobiological organisms using alternative biochemistry, for example using artificial xeno nucleic acids (XNA) instead of DNA.[135][136] Regarding auxotrophy, bacteria and yeast can be engineered to be unable to produce histidine, an important amino acid for all life. Such organisms can thus only be grown on histidine-rich media in laboratory conditions, nullifying fears that they could spread into undesirable areas.



Biosecurity 生物安全

Some ethical issues relate to biosecurity, where biosynthetic technologies could be deliberately used to cause harm to society and/or the environment. Since synthetic biology raises ethical issues and biosecurity issues, humanity must consider and plan on how to deal with potentially harmful creations, and what kinds of ethical measures could possibly be employed to deter nefarious biosynthetic technologies. With the exception of regulating synthetic biology and biotechnology companies,[137][138] however, the issues are not seen as new because they were raised during the earlier recombinant DNA and genetically modified organism (GMO) debates and extensive regulations of genetic engineering and pathogen research are already in place in many jurisdictions.[139]


European Union 欧盟方面

The European Union-funded project SYNBIOSAFE[140] has issued reports on how to manage synthetic biology. A 2007 paper identified key issues in safety, security, ethics and the science-society interface, which the project defined as public education and ongoing dialogue among scientists, businesses, government and ethicists.[141][142] The key security issues that SYNBIOSAFE identified involved engaging companies that sell synthetic DNA and the biohacking community of amateur biologists. Key ethical issues concerned the creation of new life forms.


A subsequent report focused on biosecurity, especially the so-called dual-use challenge. For example, while synthetic biology may lead to more efficient production of medical treatments, it may also lead to synthesis or modification of harmful pathogens (e.g., smallpox).[143] The biohacking community remains a source of special concern, as the distributed and diffuse nature of open-source biotechnology makes it difficult to track, regulate or mitigate potential concerns over biosafety and biosecurity.[144]


COSY, another European initiative, focuses on public perception and communication.[145][146][147] To better communicate synthetic biology and its societal ramifications to a broader public, COSY and SYNBIOSAFE published SYNBIOSAFE, a 38-minute documentary film, in October 2009.[148]


The International Association Synthetic Biology has proposed self-regulation.[149] This proposes specific measures that the synthetic biology industry, especially DNA synthesis companies, should implement. In 2007, a group led by scientists from leading DNA-synthesis companies published a "practical plan for developing an effective oversight framework for the DNA-synthesis industry".[137]


United States 美国方面

In January 2009, the Alfred P. Sloan Foundation funded the Woodrow Wilson Center, the Hastings Center, and the J. Craig Venter Institute to examine the public perception, ethics and policy implications of synthetic biology.[150]


On July 9–10, 2009, the National Academies' Committee of Science, Technology & Law convened a symposium on "Opportunities and Challenges in the Emerging Field of Synthetic Biology".[151]


After the publication of the first synthetic genome and the accompanying media coverage about "life" being created, President Barack Obama established the Presidential Commission for the Study of Bioethical Issues to study synthetic biology.[152] The commission convened a series of meetings, and issued a report in December 2010 titled "New Directions: The Ethics of Synthetic Biology and Emerging Technologies." The commission stated that "while Venter’s achievement marked a significant technical advance in demonstrating that a relatively large genome could be accurately synthesized and substituted for another, it did not amount to the “creation of life”.[153] It noted that synthetic biology is an emerging field, which creates potential risks and rewards. The commission did not recommend policy or oversight changes and called for continued funding of the research and new funding for monitoring, study of emerging ethical issues and public education.[139]


Synthetic biology, as a major tool for biological advances, results in the "potential for developing biological weapons, possible unforeseen negative impacts on human health ... and any potential environmental impact".[154] These security issues may be avoided by regulating industry uses of biotechnology through policy legislation. Federal guidelines on genetic manipulation are being proposed by "the President's Bioethics Commission ... in response to the announced creation of a self-replicating cell from a chemically synthesized genome, put forward 18 recommendations not only for regulating the science ... for educating the public".[154]


Opposition 反对意见

On March 13, 2012, over 100 environmental and civil society groups, including Friends of the Earth, the International Center for Technology Assessment and the ETC Group issued the manifesto The Principles for the Oversight of Synthetic Biology. This manifesto calls for a worldwide moratorium on the release and commercial use of synthetic organisms until more robust regulations and rigorous biosafety measures are established. The groups specifically call for an outright ban on the use of synthetic biology on the human genome or human microbiome.[155][156] Richard Lewontin wrote that some of the safety tenets for oversight discussed in The Principles for the Oversight of Synthetic Biology are reasonable, but that the main problem with the recommendations in the manifesto is that "the public at large lacks the ability to enforce any meaningful realization of those recommendations".[157]


Health and safety 健康和安全


The hazards of synthetic biology include biosafety hazards to workers and the public, biosecurity hazards stemming from deliberate engineering of organisms to cause harm, and environmental hazards. The biosafety hazards are similar to those for existing fields of biotechnology, mainly exposure to pathogens and toxic chemicals, although novel synthetic organisms may have novel risks.[158][135] For biosecurity, there is concern that synthetic or redesigned organisms could theoretically be used for bioterrorism. Potential risks include recreating known pathogens from scratch, engineering existing pathogens to be more dangerous, and engineering microbes to produce harmful biochemicals.[159] Lastly, environmental hazards include adverse effects on biodiversity and ecosystem services, including potential changes to land use resulting from agricultural use of synthetic organisms.[160][161]


Existing risk analysis systems for GMOs are generally considered sufficient for synthetic organisms, although there may be difficulties for an organism built "bottom-up" from individual genetic sequences.[136][162] Synthetic biology generally falls under existing regulations for GMOs and biotechnology in general, and any regulations that exist for downstream commercial products, although there are generally no regulations in any jurisdiction that are specific to synthetic biology.[163][164]


See also 请参阅

模板:Colbegin

Category:Biotechnology

类别: 生物技术

Category:Molecular genetics

类别: 分子遗传学

Category:Systems biology

分类: 系统生物学

Category:Bioinformatics

类别: 生物信息学

Category:Biocybernetics

类别: 生物控制论

Category:Appropriate technology

类别: 适当的技术

Category:Emerging technologies

类别: 新兴技术


This page was moved from wikipedia:en:Synthetic biology. Its edit history can be viewed at 合成生物学/edithistory

  1. Bueso, F. Y.; Tangney, M. (2017). "Synthetic Biology in the Driving Seat of the Bioeconomy". Trends in Biotechnology. 35 (5): 373–378. doi:10.1016/j.tibtech.2017.02.002. PMID 28249675.
  2. Hunter, D (2013). "How to object to radically new technologies on the basis of justice: the case of synthetic biology". Bioethics. 27 (8): 426–434. doi:10.1111/bioe.12049. PMID 24010854.
  3. Hunter, D (2013). "How to object to radically new technologies on the basis of justice: the case of synthetic biology". Bioethics. 27 (8): 426–434. doi:10.1111/bioe.12049. PMID 24010854.
  4. Gutmann, A (2011). "The ethics of synthetic biology: guiding principles for emerging technologies". Hastings Center Report. 41 (4): 17–22. doi:10.1002/j.1552-146x.2011.tb00118.x. PMID 21845917. Unknown parameter |s2cid= ignored (help)
  5. Nakano, Tadashi; Eckford, Andrew W.; Haraguchi, Tokuko (12 September 2013). [[[:模板:Google books]] Molecular Communication]. Cambridge University Press. ISBN 978-1-107-02308-6. 模板:Google books. 
  6. "Productive Nanosystems: A Technology Roadmap" (PDF). Foresight Institute.
  7. Schwille P (September 2011). "Bottom-up synthetic biology: engineering in a tinkerer's world". Science. 333 (6047): 1252–4. Bibcode:2011Sci...333.1252S. doi:10.1126/science.1211701. PMID 21885774. Unknown parameter |s2cid= ignored (help)
  8. Noireaux V, Libchaber A (December 2004). "A vesicle bioreactor as a step toward an artificial cell assembly". Proceedings of the National Academy of Sciences of the United States of America. 101 (51): 17669–74. Bibcode:2004PNAS..10117669N. doi:10.1073/pnas.0408236101. PMC 539773. PMID 15591347.
  9. Hodgman CE, Jewett MC (May 2012). "Cell-free synthetic biology: thinking outside the cell". Metabolic Engineering. 14 (3): 261–9. doi:10.1016/j.ymben.2011.09.002. PMC 3322310. PMID 21946161.
  10. Elani Y, Law RV, Ces O (June 2015). "Protein synthesis in artificial cells: using compartmentalisation for spatial organisation in vesicle bioreactors". Physical Chemistry Chemical Physics. 17 (24): 15534–7. Bibcode:2015PCCP...1715534E. doi:10.1039/C4CP05933F. PMID 25932977.
  11. Elani Y, Trantidou T, Wylie D, Dekker L, Polizzi K, Law RV, Ces O (March 2018). "Constructing vesicle-based artificial cells with embedded living cells as organelle-like modules". Scientific Reports. 8 (1): 4564. Bibcode:2018NatSR...8.4564E. doi:10.1038/s41598-018-22263-3. PMC 5852042. PMID 29540757.
  12. Lentini R, Martín NY, Forlin M, Belmonte L, Fontana J, Cornella M, Martini L, Tamburini S, Bentley WE, Jousson O, Mansy SS (February 2017). "Two-Way Chemical Communication between Artificial and Natural Cells". ACS Central Science. 3 (2): 117–123. doi:10.1021/acscentsci.6b00330. PMC 5324081. PMID 28280778.
  13. Théorie physico-chimique de la vie et générations spontanées, S. Leduc, 1910
  14. Leduc, Stéphane (1912). La biologie synthétique, étude de biophysique. http://www.peiresc.org/bstitre.htm. 
  15. Jacob, F.ß. & Monod, J. On the regulation of gene activity. Cold Spring Harb. Symp. Quant. Biol. 26, 193–211 (1961).
  16. Cohen SN, Chang AC, Boyer HW, Helling RB (1973). "Construction of biologically functional bacterial plasmids in vitro". Proc. Natl. Acad. Sci. USA. 70 (11): 3240–3244. Bibcode:1973PNAS...70.3240C. doi:10.1073/pnas.70.11.3240. PMC 427208. PMID 4594039.
  17. Szybalski W, Skalka A (November 1978). "Nobel prizes and restriction enzymes". Gene. 4 (3): 181–2. doi:10.1016/0378-1119(78)90016-1. PMID 744485.
  18. Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA (1988). "Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase". Science. 239 (4839): 487–491. doi:10.1126/science.239.4839.487. PMID 2448875.
  19. 19.0 19.1 Elowitz MB, Leibler S (January 2000). "A synthetic oscillatory network of transcriptional regulators". Nature. 403 (6767): 335–8. Bibcode:2000Natur.403..335E. doi:10.1038/35002125. PMID 10659856. Unknown parameter |s2cid= ignored (help)
  20. 20.0 20.1 Gardner TS, Cantor CR, Collins JJ (January 2000). "Construction of a genetic toggle switch in Escherichia coli". Nature. 403 (6767): 339–42. Bibcode:2000Natur.403..339G. doi:10.1038/35002131. PMID 10659857. Unknown parameter |s2cid= ignored (help)
  21. Knight, Thomas (2003). "Tom Knight (2003). Idempotent Vector Design for Standard Assembly of Biobricks". hdl:1721.1/21168. Unknown parameter |name-list-style= ignored (help); Cite journal requires |journal= (help)
  22. Martin, V. J., Pitera, D. J., Withers, S. T., Newman, J. D. & Keasling, J. D. Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Nature Biotech. 21, 796–802 (2003).
  23. Levskaya, A.; et al. (2005). ""Synthetic biology " engineering Escherichia coli to see light". Nature. 438 (7067): 441–442. doi:10.1038/nature04405. PMID 16306980. Unknown parameter |s2cid= ignored (help)
  24. Basu, S., Gerchman, Y., Collins, C. H., Arnold, F. H. & Weiss, R. "A synthetic multicellular system for programmed pattern formation. Nature 434,
  25. Anderson, J. C.; Clarke, E. J.; Arkin, A. P.; Voigt, C. A. (2006). "Environmentally controlled invasion of cancer cells by engineered bacteria". J. Mol. Biol. 355 (4): 619–627. doi:10.1016/j.jmb.2005.10.076. PMID 16330045.
  26. 26.0 26.1 Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang RY, Algire MA, Benders GA, Montague MG, Ma L, Moodie MM, Merryman C, Vashee S, Krishnakumar R, Assad-Garcia N, Andrews-Pfannkoch C, Denisova EA, Young L, Qi ZQ, Segall-Shapiro TH, Calvey CH, Parmar PP, Hutchison CA, Smith HO, Venter JC (July 2010). "Creation of a bacterial cell controlled by a chemically synthesized genome". Science. 329 (5987): 52–6. Bibcode:2010Sci...329...52G. doi:10.1126/science.1190719. PMID 20488990.
  27. "American scientist who created artificial life denies 'playing God'". The Telegraph. May 2010.
  28. Dymond, J. S.; et al. (2011). "Synthetic chromosome arms function in yeast and generate phenotypic diversity by design". Nature. 477 (7365): 816–821. doi:10.1038/nature10403. PMC 3774833. PMID 21918511.
  29. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012). "A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity". Science. 337 (6096): 816–821. doi:10.1126/science.1225829. PMC 6286148. PMID 22745249.
  30. ETH Zurich (1 April 2019). "First bacterial genome created entirely with a computer". EurekAlert!. Retrieved 2 April 2019.
  31. Venetz, Jonathan E.; et al. (1 April 2019). "Chemical synthesis rewriting of a bacterial genome to achieve design flexibility and biological functionality". Proceedings of the National Academy of Sciences of the United States of America. 116 (16): 8070–8079. doi:10.1073/pnas.1818259116. PMC 6475421. PMID 30936302.
  32. 32.0 32.1 Zimmer, Carl (15 May 2019). "Scientists Created Bacteria With a Synthetic Genome. Is This Artificial Life? - In a milestone for synthetic biology, colonies of E. coli thrive with DNA constructed from scratch by humans, not nature". The New York Times. Retrieved 16 May 2019.
  33. 33.0 33.1 Fredens, Julius; et al. (15 May 2019). "Total synthesis of Escherichia coli with a recoded genome". Nature. 569 (7757): 514–518. Bibcode:2019Natur.569..514F. doi:10.1038/s41586-019-1192-5. PMC 7039709. PMID 31092918.
  34. Zeng, Jie (Bangzhe). "On the concept of systems bio-engineering". Coomunication on Transgenic Animals, June 1994, CAS, PRC. 6.
  35. Chopra, Paras; Akhil Kamma. "Engineering life through Synthetic Biology". In Silico Biology. 6.
  36. Channon K, Bromley EH, Woolfson DN (August 2008). "Synthetic biology through biomolecular design and engineering". Current Opinion in Structural Biology. 18 (4): 491–8. doi:10.1016/j.sbi.2008.06.006. PMID 18644449.
  37. Stone, M (2006). "Life Redesigned to Suit the Engineering Crowd" (PDF). Microbe. 1 (12): 566–570. Unknown parameter |s2cid= ignored (help)
  38. Baker D, Church G, Collins J, Endy D, Jacobson J, Keasling J, Modrich P, Smolke C, Weiss R (June 2006). "Engineering life: building a fab for biology". Scientific American. 294 (6): 44–51. Bibcode:2006SciAm.294f..44B. doi:10.1038/scientificamerican0606-44. PMID 16711359.
  39. Kosuri S, Church GM (May 2014). "Large-scale de novo DNA synthesis: technologies and applications". Nature Methods. 11 (5): 499–507. doi:10.1038/nmeth.2918. PMC 7098426. PMID 24781323.
  40. Blight KJ, Kolykhalov AA, Rice CM (December 2000). "Efficient initiation of HCV RNA replication in cell culture". Science. 290 (5498): 1972–4. Bibcode:2000Sci...290.1972B. doi:10.1126/science.290.5498.1972. PMID 11110665.
  41. Couzin J (July 2002). "Virology. Active poliovirus baked from scratch". Science. 297 (5579): 174–5. doi:10.1126/science.297.5579.174b. PMID 12114601. Unknown parameter |s2cid= ignored (help)
  42. Smith HO, Hutchison CA, Pfannkoch C, Venter JC (December 2003). "Generating a synthetic genome by whole genome assembly: phiX174 bacteriophage from synthetic oligonucleotides". Proceedings of the National Academy of Sciences of the United States of America. 100 (26): 15440–5. Bibcode:2003PNAS..10015440S. doi:10.1073/pnas.2237126100. PMC 307586. PMID 14657399.
  43. Wade, Nicholas (2007-06-29). "Scientists Transplant Genome of Bacteria". The New York Times. ISSN 0362-4331. Retrieved 2007-12-28.
  44. Gibson DG, Benders GA, Andrews-Pfannkoch C, Denisova EA, Baden-Tillson H, Zaveri J, Stockwell TB, Brownley A, Thomas DW, Algire MA, Merryman C, Young L, Noskov VN, Glass JI, Venter JC, Hutchison CA, Smith HO (February 2008). "Complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium genome". Science. 319 (5867): 1215–20. Bibcode:2008Sci...319.1215G. doi:10.1126/science.1151721. PMID 18218864. Unknown parameter |s2cid= ignored (help)
  45. Ball, Philip (2016). "Man Made: A History of Synthetic Life". Distillations. 2 (1): 15–23. Retrieved 22 March 2018.
  46. Pollack, Andrew (2007-09-12). "How Do You Like Your Genes? Biofabs Take Orders". The New York Times. ISSN 0362-4331. Retrieved 2007-12-28.
  47. "Synthetic Biology Projects". arep.med.harvard.edu. Retrieved 2018-02-17.
  48. Forster AC, Church GM (2006-08-22). "Towards synthesis of a minimal cell". Molecular Systems Biology. 2 (1): 45. doi:10.1038/msb4100090. PMC 1681520. PMID 16924266.
  49. 49.0 49.1 Basulto, Dominic (November 4, 2015). "Everything you need to know about why CRISPR is such a hot technology". Washington Post. Retrieved 5 December 2015.
  50. Kahn, Jennifer (November 9, 2015). "The Crispr Quandary". New York Times. Retrieved 5 December 2015.
  51. Ledford, Heidi (June 3, 2015). "CRISPR, the disruptor". Nature. Nature News. 522 (7554): 20–4. Bibcode:2015Natur.522...20L. doi:10.1038/522020a. PMID 26040877. Retrieved 5 December 2015.
  52. Higginbotham, Stacey (4 December 2015). "Top VC Says Gene Editing Is Riskier Than Artificial Intelligence". Fortune. Retrieved 5 December 2015.
  53. Rollie; et al. (2012). "Designing biological systems: Systems Engineering meets Synthetic Biology". Chemical Engineering Science. 69 (1): 1–29. doi:10.1016/j.ces.2011.10.068.
  54. Elani Y (June 2016). "Construction of membrane-bound artificial cells using microfluidics: a new frontier in bottom-up synthetic biology". Biochemical Society Transactions. 44 (3): 723–30. doi:10.1042/BST20160052. PMC 4900754. PMID 27284034.
  55. Gach PC, Iwai K, Kim PW, Hillson NJ, Singh AK (October 2017). "Droplet microfluidics for synthetic biology". Lab on a Chip. 17 (20): 3388–3400. doi:10.1039/C7LC00576H. OSTI 1421856. PMID 28820204.
  56. Vinuselvi P, Park S, Kim M, Park JM, Kim T, Lee SK (2011-06-03). "Microfluidic technologies for synthetic biology". International Journal of Molecular Sciences. 12 (6): 3576–93. doi:10.3390/ijms12063576. PMC 3131579. PMID 21747695.
  57. 57.0 57.1 Freemont, Paul S.; Kitney, Richard I. (2012). Synthetic Biology – A Primer. World Scientific. doi:10.1142/p837. ISBN 978-1-84816-863-3. 
  58. Knight, Thomas (2003). "Tom Knight (2003). Idempotent Vector Design for Standard Assembly of Biobricks". hdl:1721.1/21168. Unknown parameter |name-list-style= ignored (help); Cite journal requires |journal= (help)
  59. Woolfson DN, Bartlett GJ, Bruning M, Thomson AR (August 2012). "New currency for old rope: from coiled-coil assemblies to α-helical barrels". Current Opinion in Structural Biology. 22 (4): 432–41. doi:10.1016/j.sbi.2012.03.002. PMID 22445228.
  60. Dueber JE, Wu GC, Malmirchegini GR, Moon TS, Petzold CJ, Ullal AV, Prather KL, Keasling JD (August 2009). "Synthetic protein scaffolds provide modular control over metabolic flux". Nature Biotechnology. 27 (8): 753–9. doi:10.1038/nbt.1557. PMID 19648908. Unknown parameter |s2cid= ignored (help)
  61. Reddington SC, Howarth M (December 2015). "Secrets of a covalent interaction for biomaterials and biotechnology: SpyTag and SpyCatcher". Current Opinion in Chemical Biology. 29: 94–9. doi:10.1016/j.cbpa.2015.10.002. PMID 26517567.
  62. Bayle JH, Grimley JS, Stankunas K, Gestwicki JE, Wandless TJ, Crabtree GR (January 2006). "Rapamycin analogs with differential binding specificity permit orthogonal control of protein activity". Chemistry & Biology. 13 (1): 99–107. doi:10.1016/j.chembiol.2005.10.017. PMID 16426976.
  63. Altszyler E, Ventura A, Colman-Lerner A, Chernomoretz A (October 2014). "Impact of upstream and downstream constraints on a signaling module's ultrasensitivity". Physical Biology. 11 (6): 066003. Bibcode:2014PhBio..11f6003A. doi:10.1088/1478-3975/11/6/066003. PMC 4233326. PMID 25313165.
  64. Altszyler E, Ventura AC, Colman-Lerner A, Chernomoretz A (2017). "Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations". PLOS ONE. 12 (6): e0180083. arXiv:1608.08007. Bibcode:2017PLoSO..1280083A. doi:10.1371/journal.pone.0180083. PMC 5491127. PMID 28662096.
  65. Carbonell-Ballestero M, Duran-Nebreda S, Montañez R, Solé R, Macía J, Rodríguez-Caso C (December 2014). "A bottom-up characterization of transfer functions for synthetic biology designs: lessons from enzymology". Nucleic Acids Research. 42 (22): 14060–14069. doi:10.1093/nar/gku964. PMC 4267673. PMID 25404136.
  66. Kaznessis YN (November 2007). "Models for synthetic biology". BMC Systems Biology. 1 (1): 47. doi:10.1186/1752-0509-1-47. PMC 2194732. PMID 17986347.
  67. Tuza ZA, Singhal V, Kim J, Murray RM (December 2013). "An in silico modeling toolbox for rapid prototyping of circuits in a biomolecular "breadboard" system.". 52nd IEEE Conference on Decision and Control. doi:10.1109/CDC.2013.6760079.
  68. 68.0 68.1 Khalil AS, Lu TK, Bashor CJ, Ramirez CL, Pyenson NC, Joung JK, Collins JJ (August 2012). "A synthetic biology framework for programming eukaryotic transcription functions". Cell. 150 (3): 647–58. doi:10.1016/j.cell.2012.05.045. PMC 3653585. PMID 22863014.
  69. Singh V (December 2014). "Recent advances and opportunities in synthetic logic gates engineering in living cells". Systems and Synthetic Biology. 8 (4): 271–82. doi:10.1007/s11693-014-9154-6. PMC 4571725. PMID 26396651.
  70. Purcell O, Lu TK (October 2014). "Synthetic analog and digital circuits for cellular computation and memory". Current Opinion in Biotechnology. Cell and Pathway Engineering. 29: 146–55. doi:10.1016/j.copbio.2014.04.009. PMC 4237220. PMID 24794536.
  71. Daniel R, Rubens JR, Sarpeshkar R, Lu TK (May 2013). "Synthetic analog computation in living cells". Nature. 497 (7451): 619–23. Bibcode:2013Natur.497..619D. doi:10.1038/nature12148. PMID 23676681. Unknown parameter |s2cid= ignored (help)
  72. Rinaudo K, Bleris L, Maddamsetti R, Subramanian S, Weiss R, Benenson Y (July 2007). "A universal RNAi-based logic evaluator that operates in mammalian cells". Nature Biotechnology. 25 (7): 795–801. doi:10.1038/nbt1307. PMID 17515909. Unknown parameter |s2cid= ignored (help)
  73. Xie Z, Wroblewska L, Prochazka L, Weiss R, Benenson Y (September 2011). "Multi-input RNAi-based logic circuit for identification of specific cancer cells". Science. 333 (6047): 1307–11. Bibcode:2011Sci...333.1307X. doi:10.1126/science.1205527. PMID 21885784. Unknown parameter |s2cid= ignored (help)
  74. Nielsen AA, Der BS, Shin J, Vaidyanathan P, Paralanov V, Strychalski EA, Ross D, Densmore D, Voigt CA (April 2016). "Genetic circuit design automation". Science. 352 (6281): aac7341. doi:10.1126/science.aac7341. PMID 27034378.
  75. Weinberg BH, Pham NT, Caraballo LD, Lozanoski T, Engel A, Bhatia S, Wong WW (May 2017). "Large-scale design of robust genetic circuits with multiple inputs and outputs for mammalian cells". Nature Biotechnology. 35 (5): 453–462. doi:10.1038/nbt.3805. PMC 5423837. PMID 28346402.
  76. de Almeida PE, van Rappard JR, Wu JC (September 2011). "In vivo bioluminescence for tracking cell fate and function". American Journal of Physiology. Heart and Circulatory Physiology. 301 (3): H663–71. doi:10.1152/ajpheart.00337.2011. PMC 3191083. PMID 21666118.
  77. Close DM, Xu T, Sayler GS, Ripp S (2011). "In vivo bioluminescent imaging (BLI): noninvasive visualization and interrogation of biological processes in living animals". Sensors. 11 (1): 180–206. doi:10.3390/s110100180. PMC 3274065. PMID 22346573.
  78. Gibbs, W. Wayt (1997). "Critters on a Chip". Scientific American. Retrieved 2 Mar 2009. Unknown parameter |name-list-style= ignored (help)
  79. Belkin, Shimshon; Yagur-Kroll, Sharon; Kabessa, Yossef; Korouma, Victor; Septon, Tali; Anati, Yonatan; Zohar-Perez, Cheinat; Rabinovitz, Zahi; Nussinovitch, Amos (April 2017). "Remote detection of buried landmines using a bacterial sensor". Nature Biotechnology. 35 (4): 308–310. doi:10.1038/nbt.3791. ISSN 1087-0156. PMID 28398330. Unknown parameter |s2cid= ignored (help)
  80. Danino T, Prindle A, Kwong GA, Skalak M, Li H, Allen K, Hasty J, Bhatia SN (May 2015). "Programmable probiotics for detection of cancer in urine". Science Translational Medicine. 7 (289): 289ra84. doi:10.1126/scitranslmed.aaa3519. PMC 4511399. PMID 26019220.
  81. Westfall PJ, Pitera DJ, Lenihan JR, Eng D, Woolard FX, Regentin R, Horning T, Tsuruta H, Melis DJ, Owens A, Fickes S, Diola D, Benjamin KR, Keasling JD, Leavell MD, McPhee DJ, Renninger NS, Newman JD, Paddon CJ (January 2012). "Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin". Proceedings of the National Academy of Sciences of the United States of America. 109 (3): E111–8. Bibcode:2012PNAS..109E.111W. doi:10.1073/pnas.1110740109. PMC 3271868. PMID 22247290.
  82. Connor, Steve (28 March 2014). "Eureka! Scientists unveil giant leap towards synthetic life". The Independent. Retrieved 2015-08-06.
  83. Nguyen PQ, Botyanszki Z, Tay PK, Joshi NS (September 2014). "Programmable biofilm-based materials from engineered curli nanofibres". Nature Communications. 5: 4945. Bibcode:2014NatCo...5.4945N. doi:10.1038/ncomms5945. PMID 25229329.
  84. Kuhlman B, Dantas G, Ireton GC, Varani G, Stoddard BL, Baker D (November 2003). "Design of a novel globular protein fold with atomic-level accuracy". Science. 302 (5649): 1364–8. Bibcode:2003Sci...302.1364K. doi:10.1126/science.1089427. PMID 14631033. Unknown parameter |s2cid= ignored (help)
  85. Koder RL, Anderson JL, Solomon LA, Reddy KS, Moser CC, Dutton PL (March 2009). "Design and engineering of an O(2) transport protein". Nature. 458 (7236): 305–9. Bibcode:2009Natur.458..305K. doi:10.1038/nature07841. PMC 3539743. PMID 19295603.
  86. Farid TA, Kodali G, Solomon LA, Lichtenstein BR, Sheehan MM, Fry BA, Bialas C, Ennist NM, Siedlecki JA, Zhao Z, Stetz MA, Valentine KG, Anderson JL, Wand AJ, Discher BM, Moser CC, Dutton PL (December 2013). "Elementary tetrahelical protein design for diverse oxidoreductase functions". Nature Chemical Biology. 9 (12): 826–833. doi:10.1038/nchembio.1362. PMC 4034760. PMID 24121554.
  87. Wang, MS; Hecht, MH (2020). "A Completely De Novo ATPase from Combinatorial Protein Design". Journal of the American Chemical Society. 142 (36): 15230–15234. doi:10.1021/jacs.0c02954. ISSN 0002-7863. PMID 32833456.
  88. Armbruster BN, Li X, Pausch MH, Herlitze S, Roth BL (March 2007). "Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand". Proceedings of the National Academy of Sciences of the United States of America. 104 (12): 5163–8. Bibcode:2007PNAS..104.5163A. doi:10.1073/pnas.0700293104. PMC 1829280. PMID 17360345.
  89. Mak WS, Tran S, Marcheschi R, Bertolani S, Thompson J, Baker D, Liao JC, Siegel JB (November 2015). "Integrative genomic mining for enzyme function to enable engineering of a non-natural biosynthetic pathway". Nature Communications. 6: 10005. Bibcode:2015NatCo...610005M. doi:10.1038/ncomms10005. PMC 4673503. PMID 26598135.
  90. Wang Q, Parrish AR, Wang L (March 2009). "Expanding the genetic code for biological studies". Chemistry & Biology. 16 (3): 323–36. doi:10.1016/j.chembiol.2009.03.001. PMC 2696486. PMID 19318213.
  91. Davidson, AR; Lumb, KJ; Sauer, RT (1995). "Cooperatively folded proteins in random sequence libraries". Nature Structural Biology. 2 (10): 856–864. doi:10.1038/nsb1095-856. PMID 7552709. Unknown parameter |s2cid= ignored (help)
  92. Kamtekar S, Schiffer JM, Xiong H, Babik JM, Hecht MH (December 1993). "Protein design by binary patterning of polar and nonpolar amino acids". Science. 262 (5140): 1680–5. Bibcode:1993Sci...262.1680K. doi:10.1126/science.8259512. PMID 8259512.
  93. Walter KU, Vamvaca K, Hilvert D (November 2005). "An active enzyme constructed from a 9-amino acid alphabet". The Journal of Biological Chemistry. 280 (45): 37742–6. doi:10.1074/jbc.M507210200. PMID 16144843.
  94. "Synthetic Biology Applications". www.thermofisher.com. Retrieved 2015-11-12.
  95. Liu Y, Shin HD, Li J, Liu L (February 2015). "Toward metabolic engineering in the context of system biology and synthetic biology: advances and prospects". Applied Microbiology and Biotechnology. 99 (3): 1109–18. doi:10.1007/s00253-014-6298-y. PMID 25547833. Unknown parameter |s2cid= ignored (help)
  96. Church GM, Gao Y, Kosuri S (September 2012). "Next-generation digital information storage in DNA". Science. 337 (6102): 1628. Bibcode:2012Sci...337.1628C. doi:10.1126/science.1226355. PMID 22903519. Unknown parameter |s2cid= ignored (help)
  97. "Huge amounts of data can be stored in DNA". Sky News. 23 January 2013. Archived from the original on 2016-05-31. Retrieved 24 January 2013.
  98. Zadeh, Joseph N.; Steenberg, Conrad D.; Bois, Justin S.; Wolfe, Brian R.; Pierce, Marshall B.; Khan, Asif R.; Dirks, Robert M.; Pierce, Niles A. (2011-01-15). "NUPACK: Analysis and design of nucleic acid systems". Journal of Computational Chemistry (in English). 32 (1): 170–173. doi:10.1002/jcc.21596. PMID 20645303.
  99. Lorenz, Ronny; Bernhart, Stephan H.; Höner zu Siederdissen, Christian; Tafer, Hakim; Flamm, Christoph; Stadler, Peter F.; Hofacker, Ivo L. (2011-11-24). "ViennaRNA Package 2.0". Algorithms for Molecular Biology (in English). 6 (1): 26. doi:10.1186/1748-7188-6-26. ISSN 1748-7188. PMC 3319429. PMID 22115189.
  100. Salis, Howard M.; Mirsky, Ethan A.; Voigt, Christopher A. (October 2009). "Automated design of synthetic ribosome binding sites to control protein expression". Nature Biotechnology (in English). 27 (10): 946–950. doi:10.1038/nbt.1568. ISSN 1546-1696. PMC 2782888. PMID 19801975.
  101. Nielsen, A. A. K.; Der, B. S.; Shin, J.; Vaidyanathan, P.; Paralanov, V.; Strychalski, E. A.; Ross, D.; Densmore, D.; Voigt, C. A. (2016-04-01). "Genetic circuit design automation". Science (in English). 352 (6281): aac7341. doi:10.1126/science.aac7341. ISSN 0036-8075. PMID 27034378.
  102. Hossain, Ayaan; Lopez, Eriberto; Halper, Sean M.; Cetnar, Daniel P.; Reis, Alexander C.; Strickland, Devin; Klavins, Eric; Salis, Howard M. (2020-07-13). "Automated design of thousands of nonrepetitive parts for engineering stable genetic systems". Nature Biotechnology (in English): 1–10. doi:10.1038/s41587-020-0584-2. ISSN 1546-1696. PMID 32661437. Unknown parameter |s2cid= ignored (help)
  103. Pollack, Andrew (May 7, 2014). "Researchers Report Breakthrough in Creating Artificial Genetic Code". New York Times. Retrieved May 7, 2014.
  104. Callaway, Ewen (May 7, 2014). "First life with 'alien' DNA". Nature. doi:10.1038/nature.2014.15179. Retrieved May 7, 2014. Unknown parameter |s2cid= ignored (help)
  105. 105.0 105.1 Malyshev DA, Dhami K, Lavergne T, Chen T, Dai N, Foster JM, Corrêa IR, Romesberg FE (May 2014). "A semi-synthetic organism with an expanded genetic alphabet". Nature. 509 (7500): 385–8. Bibcode:2014Natur.509..385M. doi:10.1038/nature13314. PMC 4058825. PMID 24805238.
  106. 106.0 106.1 Verseux, C.; Paulino-Lima, I.; Baque, M.; Billi, D.; Rothschild, L. (2016). Synthetic Biology for Space Exploration: Promises and Societal Implications. Ethics of Science and Technology Assessment. 45. pp. 73–100. doi:10.1007/978-3-319-21088-9_4. ISBN 978-3-319-21087-2. 
  107. Menezes, A; Cumbers, J; Hogan, J; Arkin, A (2014). "Towards synthetic biological approaches to resource utilization on space missions". Journal of the Royal Society, Interface. 12 (102): 20140715. doi:10.1098/rsif.2014.0715. PMC 4277073. PMID 25376875.
  108. Montague M, McArthur GH, Cockell CS, Held J, Marshall W, Sherman LA, Wang N, Nicholson WL, Tarjan DR, Cumbers J (December 2012). "The role of synthetic biology for in situ resource utilization (ISRU)". Astrobiology. 12 (12): 1135–42. Bibcode:2012AsBio..12.1135M. doi:10.1089/ast.2012.0829. PMID 23140229.
  109. GSFC, Bill Steigerwald. "NASA - Designer Plants on Mars". www.nasa.gov (in English). Retrieved 2020-05-29.
  110. Hutchison CA, Chuang RY, Noskov VN, Assad-Garcia N, Deerinck TJ, Ellisman MH, Gill J, Kannan K, Karas BJ, Ma L, Pelletier JF, Qi ZQ, Richter RA, Strychalski EA, Sun L, Suzuki Y, Tsvetanova B, Wise KS, Smith HO, Glass JI, Merryman C, Gibson DG, Venter JC (March 2016). "Design and synthesis of a minimal bacterial genome". Science. 351 (6280): aad6253. Bibcode:2016Sci...351.....H. doi:10.1126/science.aad6253. PMID 27013737.
  111. 111.0 111.1 Connor, Steve (1 December 2014). "Major synthetic life breakthrough as scientists make the first artificial enzymes". The Independent. London. Retrieved 2015-08-06.
  112. 112.0 112.1 Deamer D (July 2005). "A giant step towards artificial life?". Trends in Biotechnology. 23 (7): 336–8. doi:10.1016/j.tibtech.2005.05.008. PMID 15935500.
  113. "Scientists Reach Milestone On Way To Artificial Life". 2010-05-20. Retrieved 2010-06-09.
  114. Venter, JC. "From Designing Life to Prolonging Healthy Life". YouTube. University of California Television (UCTV). Retrieved 1 February 2017.
  115. "Build-a-Cell". Retrieved 4 Dec 2019.
  116. "FabriCell". Retrieved 8 Dec 2019.
  117. "MaxSynBio - Max Planck Research Network in Synthetic Biology". Retrieved 8 Dec 2019.
  118. "BaSyC". Retrieved 8 Dec 2019.
  119. "SynCell EU". Retrieved 8 Dec 2019.
  120. Zu C, Wang J (August 2014). "Tumor-colonizing bacteria: a potential tumor targeting therapy". Critical Reviews in Microbiology. 40 (3): 225–35. doi:10.3109/1040841X.2013.776511. PMID 23964706. Unknown parameter |s2cid= ignored (help)
  121. Gujrati V, Kim S, Kim SH, Min JJ, Choy HE, Kim SC, Jon S (February 2014). "Bioengineered bacterial outer membrane vesicles as cell-specific drug-delivery vehicles for cancer therapy". ACS Nano. 8 (2): 1525–37. doi:10.1021/nn405724x. PMID 24410085.
  122. Piñero-Lambea C, Bodelón G, Fernández-Periáñez R, Cuesta AM, Álvarez-Vallina L, Fernández LÁ (April 2015). "Programming controlled adhesion of E. coli to target surfaces, cells, and tumors with synthetic adhesins". ACS Synthetic Biology. 4 (4): 463–73. doi:10.1021/sb500252a. PMC 4410913. PMID 25045780.
  123. Deyneko, I.V.; Kasnitz, N.; Leschner, S.; Weiss, S. (2016). "Composing a tumor specific bacterial promoter". PLOS ONE. 11 (5): e0155338. doi:10.1371/journal.pone.0155338. PMC 4865170. PMID 27171245.
  124. Rice, KC; Bayles, KW (2008). "Molecular control of bacterial death and lysis". Microbiol Mol Biol Rev. 72 (1): 85–109. doi:10.1128/mmbr.00030-07. PMC 2268280. PMID 18322035.
  125. Ganai, S.; Arenas, R. B.; Forbes, N. S. (2009). "Tumour-targeted delivery of TRAIL using Salmonella typhimurium enhances breast cancer survival in mice". Br. J. Cancer. 101 (10): 1683–1691. doi:10.1038/sj.bjc.6605403. PMC 2778534. PMID 19861961.
  126. Jones, B.S., Lamb, L.S., Goldman, F. & Di Stasi, A. Improving the safety of cell therapy products by suicide gene transfer. Front. Pharmacol. 5, 254 (2014).
  127. Wei, P; Wong, WW; Park, JS; Corcoran, EE; Peisajovich, SG; Onuffer, JJ; Weiss, A; LiWA (2012). "Bacterial virulence proteins as tools to rewire kinase pathways in yeast and immune cells". Nature. 488 (7411): 384–388. doi:10.1038/nature11259. PMC 3422413. PMID 22820255.
  128. Danino, T.; Mondragon-Palomino, O.; Tsimring, L.; Hasty, J. (2010). "A synchronized quorum of genetic clocks". Nature. 463 (7279): 326–330. doi:10.1038/nature08753. PMC 2838179. PMID 20090747.
  129. Chen, Y. Y.; Jensen, M. C.; Smolke, C. D. (2010). "Genetic control of mammalian T-cell proliferation with synthetic RNA regulatory systems". Proc. Natl. Acad. Sci. U.S.A. 107 (19): 8531–6. doi:10.1073/pnas.1001721107. PMC 2889348. PMID 20421500.
  130. 130.0 130.1 130.2 Newson, AJ (2015). "Synthetic Biology: Ethics, Exeptionalism and Expectations". Macquarie Law Journal. 15: 45.
  131. Staff, Agencies (November 2018). "World's first gene-edited babies created in China, claims scientist". The Guardian.
  132. Hayry, Mattie (April 2017). "Synthetic Biology and Ethics: Past, Present, and Future". Cambridge Quarterly of Healthcare Ethics. 26 (2): 186–205. doi:10.1017/S0963180116000803. PMID 28361718.
  133. Jin, Shan; et al. (September 2019). "Synthetic biology applied in the agrifood sector: Public perceptions, attitudes and implications for future studies". Trends in Food Science and Technology. 91: 454–466. doi:10.1016/j.tifs.2019.07.025.
  134. Amy, Gutmann (2012). "The Ethics of Synthetic Biology". The Hastings Center Report. 41 (4): 17–22. doi:10.1002/j.1552-146X.2011.tb00118.x. PMID 21845917. Unknown parameter |s2cid= ignored (help)
  135. 135.0 135.1 Howard, John; Murashov, Vladimir; Schulte, Paul (2016-10-18). "Synthetic biology and occupational risk". Journal of Occupational and Environmental Hygiene. 14 (3): 224–236. doi:10.1080/15459624.2016.1237031. ISSN 1545-9624. PMID 27754800. Unknown parameter |s2cid= ignored (help)
  136. 136.0 136.1 "Opinion on synthetic biology II: Risk assessment methodologies and safety aspects". EU Directorate-General for Health and Consumers. Publications Office. 2016-02-12. doi:10.2772/63529.
  137. 137.0 137.1 Bügl H, Danner JP, Molinari RJ, Mulligan JT, Park HO, Reichert B, Roth DA, Wagner R, Budowle B, Scripp RM, Smith JA, Steele SJ, Church G, Endy D (June 2007). "DNA synthesis and biological security". Nature Biotechnology. 25 (6): 627–9. doi:10.1038/nbt0607-627. PMID 17557094. Unknown parameter |s2cid= ignored (help)
  138. "Ethical Issues in Synthetic Biology: An Overview of the Debates" (PDF).
  139. 139.0 139.1 Presidential Commission for the study of Bioethical Issues, December 2010 NEW DIRECTIONS The Ethics of Synthetic Biology and Emerging Technologies Retrieved 2012-04-14.
  140. SYNBIOSAFE official site
  141. Schmidt M, Ganguli-Mitra A, Torgersen H, Kelle A, Deplazes A, Biller-Andorno N (December 2009). "A priority paper for the societal and ethical aspects of synthetic biology" (PDF). Systems and Synthetic Biology. 3 (1–4): 3–7. doi:10.1007/s11693-009-9034-7. PMC 2759426. PMID 19816794.
  142. Schmidt M. Kelle A. Ganguli A, de Vriend H. (Eds.) 2009. "Synthetic Biology. The Technoscience and its Societal Consequences". Springer Academic Publishing.
  143. Kelle A (December 2009). "Ensuring the security of synthetic biology-towards a 5P governance strategy". Systems and Synthetic Biology. 3 (1–4): 85–90. doi:10.1007/s11693-009-9041-8. PMC 2759433. PMID 19816803.
  144. Schmidt M (June 2008). "Diffusion of synthetic biology: a challenge to biosafety" (PDF). Systems and Synthetic Biology. 2 (1–2): 1–6. doi:10.1007/s11693-008-9018-z. PMC 2671588. PMID 19003431.
  145. COSY: Communicating Synthetic Biology
  146. Kronberger N, Holtz P, Kerbe W, Strasser E, Wagner W (December 2009). "Communicating Synthetic Biology: from the lab via the media to the broader public". Systems and Synthetic Biology. 3 (1–4): 19–26. doi:10.1007/s11693-009-9031-x. PMC 2759424. PMID 19816796.
  147. Cserer A, Seiringer A (December 2009). "Pictures of Synthetic Biology : A reflective discussion of the representation of Synthetic Biology (SB) in the German-language media and by SB experts". Systems and Synthetic Biology. 3 (1–4): 27–35. doi:10.1007/s11693-009-9038-3. PMC 2759430. PMID 19816797.
  148. COSY/SYNBIOSAFE Documentary
  149. Report of IASB "Technical solutions for biosecurity in synthetic biology" -{zh-cn:互联网档案馆; zh-tw:網際網路檔案館; zh-hk:互聯網檔案館;}-存檔,存档日期July 19, 2011,., Munich, 2008
  150. Parens E., Johnston J., Moses J. Ethical Issues in Synthetic Biology. 2009.
  151. NAS Symposium official site
  152. Presidential Commission for the study of Bioethical Issues, December 2010 FAQ
  153. Synthetic Biology F.A.Q.'s | Presidential Commission for the Study of Bioethical Issues
  154. 154.0 154.1 Erickson B, Singh R, Winters P (September 2011). "Synthetic biology: regulating industry uses of new biotechnologies". Science. 333 (6047): 1254–6. Bibcode:2011Sci...333.1254E. doi:10.1126/science.1211066. PMID 21885775. Unknown parameter |s2cid= ignored (help)
  155. Katherine Xue for Harvard Magazine. September–October 2014 Synthetic Biology’s New Menagerie
  156. Yojana Sharma for Scidev.net March 15, 2012. NGOs call for international regulation of synthetic biology
  157. The New Synthetic Biology: Who Gains? (2014-05-08), Richard C. Lewontin, New York Review of Books
  158. Howard, John; Murashov, Vladimir; Schulte, Paul (2017-01-24). "Synthetic Biology and Occupational Risk". Journal of Occupational and Environmental Hygiene. 14 (3): 224–236. doi:10.1080/15459624.2016.1237031. PMID 27754800. Retrieved 2018-11-30. Unknown parameter |s2cid= ignored (help)
  159. National Academies Of Sciences, Engineering; Division on Earth Life Studies; Board On Life, Sciences; Board on Chemical Sciences Technology; Committee on Strategies for Identifying Addressing Potential Biodefense Vulnerabilities Posed by Synthetic Biology (2018-06-19). Biodefense in the Age of Synthetic Biology. National Academies of Sciences, Engineering, and Medicine. doi:10.17226/24890. ISBN 9780309465182. PMID 30629396. 
  160. "Future Brief: Synthetic biology and biodiversity". European Commission. September 2016. pp. 14–15. Retrieved 2019-01-14.
  161. "Final opinion on synthetic biology III: Risks to the environment and biodiversity related to synthetic biology and research priorities in the field of synthetic biology". EU Directorate-General for Health and Food Safety. 2016-04-04. pp. 8, 27. Retrieved 2019-01-14.
  162. Bailey, Claire; Metcalf, Heather; Crook, Brian (2012). "Synthetic biology: A review of the technology, and current and future needs from the regulatory framework in Great Britain" (PDF). UK Health and Safety Executive. Retrieved 2018-11-29.
  163. Pei, Lei; Bar‐Yam, Shlomiya; Byers‐Corbin, Jennifer; Casagrande, Rocco; Eichler, Florentine; Lin, Allen; Österreicher, Martin; Regardh, Pernilla C.; Turlington, Ralph D. (2012), "Regulatory Frameworks for Synthetic Biology", Synthetic Biology, John Wiley & Sons, Ltd, pp. 157–226, doi:10.1002/9783527659296.ch5, ISBN 9783527659296
  164. Trump, Benjamin D. (2017-11-01). "Synthetic biology regulation and governance: Lessons from TAPIC for the United States, European Union, and Singapore". Health Policy. 121 (11): 1139–1146. doi:10.1016/j.healthpol.2017.07.010. ISSN 0168-8510. PMID 28807332.