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第1行： − 本词条由余凡尘初步翻译+ + + + − 此词条暂由彩云小译翻译，翻译字数共1157，未经人工整理和审校，带来阅读不便，请见谅。+ + − {{Use dmy dates|date=July 2018}} − [[File:GNA-T_vs._natural_DNA-T.png|thumb|[[Glycol nucleic acid]] ''(left)'' is an example of a xeno nucleic acid because it has a different backbone than DNA ''(right)''.|链接=Special:FilePath/GNA-T_vs._natural_DNA-T.png]] − '''Xeno nucleic acids''' ('''XNA''') are synthetic [[nucleic acid analogue]]s that have a different sugar backbone than the natural nucleic acids [[DNA]] and [[RNA]].<ref name="Schmidt2012">{{cite book |last=Schmidt|first=Markus | name-list-style = vanc |title=Synthetic Biology |url=https://books.google.com/books?id=lr0SgX1Hx2gC&pg=PA151|access-date=9 May 2013|year= 2012|publisher=John Wiley & Sons|isbn=978-3-527-65926-5|pages=151–}}</ref> As of 2011, at least six types of synthetic sugars have been shown to form nucleic acid backbones that can store and retrieve genetic information. Research is now being done to create synthetic polymerases to transform XNA. The study of its production and application has created a field known as [[xenobiology]]. + − Xeno nucleic acids (XNA) are synthetic nucleic acid analogues that have a different sugar backbone than the natural nucleic acids DNA and RNA. As of 2011, at least six types of synthetic sugars have been shown to form nucleic acid backbones that can store and retrieve genetic information. Research is now being done to create synthetic polymerases to transform XNA. The study of its production and application has created a field known as xenobiology.+ + − 异源核酸（XNA）是人工合成的核酸类似物，具有不同于天然核酸DNA和RNA的糖骨架。截止至2011年，已证明至少有六种合成的糖类能形成可存储和检索基因信息的核酸骨架。目前正在研究用合成的聚合酶来转化XNA。对其生产和应用的研究创造了一个被称为异源生物学的领域。 − Although the genetic information is still stored in the four canonical base pairs (unlike other [[nucleic acid analogues]]), natural DNA polymerases cannot read and duplicate this information. Thus the genetic information stored in XNA is "invisible" and therefore useless to natural DNA-based organisms.<ref name="Schmidt1">{{cite journal | vauthors = Schmidt M | title = Xenobiology: a new form of life as the ultimate biosafety tool | journal = BioEssays | volume = 32 | issue = 4 | pages = 322–331 | date = April 2010 | pmid = 20217844 | pmc = 2909387 | doi = 10.1002/bies.200900147 }}</ref>+ − Although the genetic information is still stored in the four canonical base pairs (unlike other nucleic acid analogues), natural DNA polymerases cannot read and duplicate this information. Thus the genetic information stored in XNA is "invisible" and therefore useless to natural DNA-based organisms. − − 虽然遗传信息仍然存储在四个标准碱基对（不像其他核酸类似物那样），但是天然的DNA聚合酶不能读取和复制这些信息。因此，存储在XNA中的遗传信息是“不可视的”，对于以天然DNA为基础的生物体来说是无用的。 − − ==Background== − The structure of [[DNA]] was discovered in 1953. Around the early 2000s, researchers created a number of exotic DNA-like structures, XNA. XNA is a synthetic polymer that can carry the same information as DNA, but with different molecular constituents. The "X" in XNA stands for "xeno," meaning stranger or alien, indicating the difference in the molecular structure as compared to DNA or RNA.<ref name=":1" /> − − The structure of DNA was discovered in 1953. Around the early 2000s, researchers created a number of exotic DNA-like structures, XNA. XNA is a synthetic polymer that can carry the same information as DNA, but with different molecular constituents. The "X" in XNA stands for "xeno," meaning stranger or alien, indicating the difference in the molecular structure as compared to DNA or RNA. − − DNA的结构于1953年被发现。大约在21世纪初，研究人员创造了许多奇特的类DNA结构，XNA。XNA是一种人工合成的聚合物，可以携带与DNA相同的信息，但具有不同的分子成分。XNA中的“X”代表“ xeno”，意思是外乡人或外星人，以表示其分子结构与DNA或RNA相比的差异。 − − Not much was done with XNA until the development of special polymerase [[enzyme]], capable of copying XNA from a DNA template as well as copying XNA back into DNA.<ref name=":1">{{Cite web |last=Gonzales |first=Robbie | name-list-style = vanc |title=XNA Is Synthetic DNA That's Stronger than the Real Thing |website=[[Io9]] |date=19 April 2012 |access-date=15 October 2015 |url=http://io9.com/5903221/meet-xna-the-first-synthetic-dna-that-evolves-like-the-real-thing}}</ref> Pinheiro et al. (2012), for example, has demonstrated such an XNA-capable polymerase that works on sequences of ~100bp in length.<ref name="Synthetic genetic polymers capable">{{cite journal | vauthors = Pinheiro VB, Taylor AI, Cozens C, Abramov M, Renders M, Zhang S, Chaput JC, Wengel J, Peak-Chew SY, McLaughlin SH, Herdewijn P, Holliger P | display-authors = 6 | title = Synthetic genetic polymers capable of heredity and evolution | journal = Science | volume = 336 | issue = 6079 | pages = 341–344 | date = April 2012 | pmid = 22517858 | pmc = 3362463 | doi = 10.1126/science.1217622 | bibcode = 2012Sci...336..341P }}</ref> More recently, synthetic biologists [[Philipp Holliger]] and Alexander Taylor managed to create XNAzymes, the XNA equivalent of a [[ribozyme]], enzymes made of DNA or ribonucleic acid. This demonstrates that XNAs not only store hereditary information, but can also serve as enzymes, raising the possibility that life elsewhere could have begun with something other than RNA or DNA.<ref>{{Cite web |website=[[Medical Research Council (United Kingdom)|Medical Research Council]] |title=World's first artificial enzymes created using synthetic biology |date=1 December 2014 |url=http://www.mrc.ac.uk/news/browse/world-s-first-artificial-enzymes-created-using-synthetic-biology/}}</ref> − − Not much was done with XNA until the development of special polymerase enzyme, capable of copying XNA from a DNA template as well as copying XNA back into DNA. Pinheiro et al. (2012), for example, has demonstrated such an XNA-capable polymerase that works on sequences of ~100bp in length. More recently, synthetic biologists Philipp Holliger and Alexander Taylor managed to create XNAzymes, the XNA equivalent of a ribozyme, enzymes made of DNA or ribonucleic acid. This demonstrates that XNAs not only store hereditary information, but can also serve as enzymes, raising the possibility that life elsewhere could have begun with something other than RNA or DNA. − − 在特殊的聚合酶被开发出来之前，对XNA的研究并不多，这种酶能够以DNA为模板复制出XNA，也能将XNA复制回DNA。例如皮涅罗（Pinheiro）等人在2012年的一项研究已证明了一种可以在大约100bp序列长度上工作的XNA聚合酶。最近，合成生物学家菲利普·霍利格（Philipp Holliger）和亚历山大·泰勒（Alexander Taylor）成功地创造了XNAzymes。XNAzymes相当于核酶，由DNA或核糖核酸构成。这表明，这表明XNAs不仅存储遗传信息，还可以作为酶，这提高了其他地方的生命可能起源于RNA或DNA以外物质的可能性。 − + − Strands of DNA and RNA are formed by stringing together long chains of molecules called [[nucleotide]]s. A [[nucleotide]] is made up of three chemical components: a [[phosphate]], a five-carbon sugar group (this can be either a [[deoxyribose]] sugar—which gives us the "D" in DNA—or a [[ribose]] sugar—the "R" in RNA), and one of five standard bases ([[adenine]], [[guanine]], [[cytosine]], [[thymine]] or [[uracil]]).+ − − thumb|369x369px|This image displays the differences in the sugar backbones used in XNAs compared to common and biologically used DNA and RNA. − Strands of DNA and RNA are formed by stringing together long chains of molecules called nucleotides. A nucleotide is made up of three chemical components: a phosphate, a five-carbon sugar group (this can be either a deoxyribose sugar—which gives us the "D" in DNA—or a ribose sugar—the "R" in RNA), and one of five standard bases (adenine, guanine, cytosine, thymine or uracil). − − − − The molecules that piece together to form the six xeno nucleic acids are almost identical to those of DNA and RNA, with one exception: in XNA [[nucleotide]]s, the [[deoxyribose]] and [[ribose]] sugar groups of DNA and RNA have been replaced with other chemical structures. These substitutions make XNAs functionally and structurally analogous to DNA and RNA despite being unnatural and artificial. − The molecules that piece together to form the six xeno nucleic acids are almost identical to those of DNA and RNA, with one exception: in XNA nucleotides, the deoxyribose and ribose sugar groups of DNA and RNA have been replaced with other chemical structures. These substitutions make XNAs functionally and structurally analogous to DNA and RNA despite being unnatural and artificial. − XNA exhibits a variety of structural chemical changes relative to its natural counterparts. Types of synthetic XNA created so far include:<ref name="Schmidt1" /> − * 1,5-anhydrohexitol nucleic acid (HNA) − * Cyclohexene nucleic acid (CeNA) − * Threose nucleic acid ([[Threose nucleic acid|TNA]]) − * Glycol nucleic acid ([[Glycol nucleic acid|GNA]]) − * Locked nucleic acid ([https://en.wikipedia.org/wiki/Locked_nucleic_acid]) − * Peptide nucleic acid ([[Peptide nucleic acid|PNA]]) − * FANA ([[Fluoro Arabino nucleic acid]]) − XNA exhibits a variety of structural chemical changes relative to its natural counterparts. Types of synthetic XNA created so far include:+ − * 1,5-anhydrohexitol nucleic acid (HNA) − * Cyclohexene nucleic acid (CeNA) − * Threose nucleic acid (TNA) − * Glycol nucleic acid (GNA) − * Locked nucleic acid () − * Peptide nucleic acid (PNA) − * FANA (Fluoro Arabino nucleic acid) − − 第72行：
第33行： − + − HNA could be used to potentially act as a drug that can recognize and bind to specified sequences. Scientists have been able to isolate HNAs for the possible binding of sequences that target HIV.<ref>{{Cite web |title = Polymers perform non-DNA evolution |url = http://www.rsc.org/chemistryworld/News/2012/April/xna-hna-primordial-life-dna-evolution-chemistry.asp |first=Andy |last=Extance | name-list-style = vanc |date=19 April 2012 |website = [[Royal Society of Chemistry]] |access-date = 15 October 2015}}</ref> With cyclohexene nucleic acid, research has shown that CeNAs with stereochemistry similar to the D form can create stable duplexes with itself and RNA. It was shown that CeNAs are not as stable when they form duplexes with DNA.<ref>{{cite journal | vauthors = Gu P, Schepers G, Rozenski J, Van Aerschot A, Herdewijn P | title = Base pairing properties of D- and L-cyclohexene nucleic acids (CeNA) | journal = Oligonucleotides | volume = 13 | issue = 6 | pages = 479–489 | year = 2003 | pmid = 15025914 | doi = 10.1089/154545703322860799 }}</ref> − HNA could be used to potentially act as a drug that can recognize and bind to specified sequences. Scientists have been able to isolate HNAs for the possible binding of sequences that target HIV. With cyclohexene nucleic acid, research has shown that CeNAs with stereochemistry similar to the D form can create stable duplexes with itself and RNA. It was shown that CeNAs are not as stable when they form duplexes with DNA.+ − HNA可被用作识别和结合特定序列的药物。科学家已经能够分离出HNAs，以靶向结合艾滋病毒相关的基因序列。研究表明，在存在环己烯核酸的情况下，具有类似D型立体化学结构的CeNAs可以与自身和RNA形成稳定的双链体。结果表明，当CeNAs与DNA形成双链体时，CeNAs不是很稳定。+ + − ==Implications启示== − The study of XNA is not intended to give scientists a better understanding of biological [[evolution]] as it has occurred historically, but rather to explore ways in which we can control and even reprogram the genetic makeup of biological organisms moving forward. XNA has shown significant potential in solving the current issue of [[genetic pollution]] in [[genetically modified organism]]s.<ref>{{cite journal | vauthors = Herdewijn P, Marlière P | title = Toward safe genetically modified organisms through the chemical diversification of nucleic acids | journal = Chemistry & Biodiversity | volume = 6 | issue = 6 | pages = 791–808 | date = June 2009 | pmid = 19554563 | doi = 10.1002/cbdv.200900083 | s2cid = 8572188 }}</ref> While DNA is incredibly efficient in its ability to store genetic information and lend complex biological diversity, its four-letter genetic alphabet is relatively limited. Using a genetic code of six XNAs rather than the four naturally occurring DNA nucleotide bases yields endless opportunities for genetic modification and expansion of chemical functionality.<ref>{{cite journal | vauthors = Pinheiro VB, Holliger P | title = The XNA world: progress towards replication and evolution of synthetic genetic polymers | journal = Current Opinion in Chemical Biology | volume = 16 | issue = 3–4 | pages = 245–252 | date = August 2012 | pmid = 22704981 | doi = 10.1016/j.cbpa.2012.05.198 }}</ref> − The study of XNA is not intended to give scientists a better understanding of biological evolution as it has occurred historically, but rather to explore ways in which we can control and even reprogram the genetic makeup of biological organisms moving forward. XNA has shown significant potential in solving the current issue of genetic pollution in genetically modified organisms. While DNA is incredibly efficient in its ability to store genetic information and lend complex biological diversity, its four-letter genetic alphabet is relatively limited. Using a genetic code of six XNAs rather than the four naturally occurring DNA nucleotide bases yields endless opportunities for genetic modification and expansion of chemical functionality.+ − XNA研究的目的不是为了让科学家更好地了解历史上发生过的生物进化，而是探索我们能够控制甚至重新编程生物体基因组成的方法。XNA在解决目前转基因生物的遗传污染问题上显示出巨大潜力。尽管DNA在储存遗传信息和提供复杂生物多样性方面具有令人难以置信的效率，但其四个字母的遗传密码表相对有限。使用6个XNAs的遗传密码而不是4个自然产生的DNA碱基，或将展现出基因修饰和扩展化学功能的无尽机遇。 − The development of various hypotheses and theories about XNAs have altered a key factor in our current understanding of nucleic acids: that [[heredity]] and evolution are not limited to DNA and RNA as once thought, but are simply processes that have developed from polymers capable of storing information.<ref name="Synthetic genetic polymers capable"/> Investigations into XNAs will allow for researchers to assess whether DNA and RNA are the most efficient and desirable building blocks of life, or if these two molecules were chosen randomly after evolving from a larger class of chemical ancestors.<ref>{{cite journal | vauthors = Hunter P | title = XNA marks the spot. What can we learn about the origins of life and the treatment of disease through artificial nucleic acids? | journal = EMBO Reports | volume = 14 | issue = 5 | pages = 410–413 | date = May 2013 | pmid = 23579343 | pmc = 3642382 | doi = 10.1038/embor.2013.42 }}</ref>+ + − The development of various hypotheses and theories about XNAs have altered a key factor in our current understanding of nucleic acids: that heredity and evolution are not limited to DNA and RNA as once thought, but are simply processes that have developed from polymers capable of storing information. Investigations into XNAs will allow for researchers to assess whether DNA and RNA are the most efficient and desirable building blocks of life, or if these two molecules were chosen randomly after evolving from a larger class of chemical ancestors. − 关于XNAs的各种假说和理论的发展已经改变了目前我们理解核酸的一个关键点: 遗传和进化并不是人们曾经认为的那样只局限于DNA和RNA，而仅仅是一种起源于能够储存信息的聚合物的简单过程。对于XNAs的研究将允许研究人员评估DNA和RNA是不是最有效和最理想的生命构件，或者这两种分子是不是在更大类的化学祖先进化之后被随机地选择出来的。+ − == Applications == − One theory of XNA utilization is its incorporation into medicine as a disease-fighting agent. Some enzymes and [[Antibody|antibodies]] that are currently administered for various disease treatments are broken down too quickly in the stomach or bloodstream. Because XNA is foreign and because it is believed that humans have not yet evolved the enzymes to break them down, XNAs may be able to serve as a more durable counterpart to the DNA and RNA-based treatment methodologies that are currently in use.<ref name=":0">{{Cite web|title = XNA: Synthetic DNA That Can Evolve|url = http://www.popularmechanics.com/science/health/a7636/xna-synthetic-dna-that-can-evolve-8210483/|website = [[Popular Mechanics]] |date = 19 April 2012 |access-date = 17 November 2015}}</ref> − One theory of XNA utilization is its incorporation into medicine as a disease-fighting agent. Some enzymes and antibodies that are currently administered for various disease treatments are broken down too quickly in the stomach or bloodstream. Because XNA is foreign and because it is believed that humans have not yet evolved the enzymes to break them down, XNAs may be able to serve as a more durable counterpart to the DNA and RNA-based treatment methodologies that are currently in use.+ − = = 应用 = = 一种利用XNA的理论是将其作为抗病剂纳入医学。目前，一些用于各种疾病治疗的酶和抗体在胃或血液中分解得太快。但由于XNA是外来的，而且人类尚未进化出能够分解它们的酶，因此对于目前正在使用的DNA和RNA治疗方法，XNA可能成为比它们更持久的替换物。 − Experiments with XNA have already allowed for the replacement and enlargement of this genetic alphabet, and XNAs have shown [[Complementarity (molecular biology)|complementarity]] with DNA and RNA nucleotides, suggesting potential for its transcription and recombination. One experiment conducted at the University of Florida led to the production of an XNA [[aptamer]] by the AEGIS-SELEX (artificially expanded genetic information system - systematic evolution of [[ligand]]s by exponential enrichment) method, followed by successful binding to a line of [[breast cancer]] cells.<ref>{{cite journal | vauthors = Sefah K, Yang Z, Bradley KM, Hoshika S, Jiménez E, Zhang L, Zhu G, Shanker S, Yu F, Turek D, Tan W, Benner SA | display-authors = 6 | title = In vitro selection with artificial expanded genetic information systems | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 4 | pages = 1449–1454 | date = January 2014 | pmid = 24379378 | pmc = 3910645 | doi = 10.1073/pnas.1311778111 | doi-access = free | bibcode = 2014PNAS..111.1449S }}</ref> Furthermore, experiments in the model bacterium ''[[Escherichia coli|E. coli]]'' have demonstrated the ability for XNA to serve as a biological template for DNA ''[[in vivo]].''<ref>{{cite journal | vauthors = Pezo V, Liu FW, Abramov M, Froeyen M, Herdewijn P, Marlière P | title = Binary genetic cassettes for selecting XNA-templated DNA synthesis in vivo | journal = Angewandte Chemie | volume = 52 | issue = 31 | pages = 8139–8143 | date = July 2013 | pmid = 23804524 | doi = 10.1002/anie.201303288 | url = https://lirias.kuleuven.be/handle/123456789/413046 }}</ref>+ − Experiments with XNA have already allowed for the replacement and enlargement of this genetic alphabet, and XNAs have shown complementarity with DNA and RNA nucleotides, suggesting potential for its transcription and recombination. One experiment conducted at the University of Florida led to the production of an XNA aptamer by the AEGIS-SELEX (artificially expanded genetic information system - systematic evolution of ligands by exponential enrichment) method, followed by successful binding to a line of breast cancer cells. Furthermore, experiments in the model bacterium E. coli have demonstrated the ability for XNA to serve as a biological template for DNA in vivo. − XNA实验已经可以替换和扩大遗传密码表，而且XNA已经显示出与DNA和RNA核苷酸的互补性，这表明它具有转录和重组的潜力。在佛罗里达大学进行的一项实验中，通过AEISIS-SELEX（人工扩增的遗传信息系统——通过指数富集的配体的系统进化）产生了一种XNA适配体，并成功与乳腺癌细胞系结合。此外，在大肠杆菌中的实验表明，XNA在体内具有作为DNA生物模板的能力。+ − In moving forward with genetic research on XNAs, various questions must come into consideration regarding [[biosafety]], [[biosecurity]], ethics, and governance/regulation.<ref name="Schmidt1" /> One of the key questions here is whether XNA in an ''in vivo'' setting would intermix with DNA and RNA in its natural environment, thereby rendering scientists unable to control or predict its implications in genetic [[mutation]].<ref name=":0" /> − In moving forward with genetic research on XNAs, various questions must come into consideration regarding biosafety, biosecurity, ethics, and governance/regulation. One of the key questions here is whether XNA in an in vivo setting would intermix with DNA and RNA in its natural environment, thereby rendering scientists unable to control or predict its implications in genetic mutation.+ + + − 在推进对XNAs的基因研究时，必须考虑到有关生物安全、生物防护、伦理和治理/监管的各种问题。这里的一个关键问题是，在体内环境中，XNA是否会与自然环境中的DNA和RNA混合，从而使科学家无法控制或预测其在基因突变中可能的影响。 − XNA also has potential applications to be used as [[Catalysis|catalysts]], much like RNA has the ability to be used as an [[enzyme]]. Researchers have shown XNA is able to cleave and [[Ligation (molecular biology)|ligate]] DNA, RNA and other XNA sequences, with the most activity being XNA catalyzed reactions on XNA molecules. This research may be used in determining whether DNA and RNA's role in life emerged through natural selection processes or if it was simply a coincidental occurrence.<ref>{{cite journal | vauthors = Taylor AI, Pinheiro VB, Smola MJ, Morgunov AS, Peak-Chew S, Cozens C, Weeks KM, Herdewijn P, Holliger P | display-authors = 6 | title = Catalysts from synthetic genetic polymers | journal = Nature | volume = 518 | issue = 7539 | pages = 427–430 | date = February 2015 | pmid = 25470036 | pmc = 4336857 | doi = 10.1038/nature13982 | bibcode = 2015Natur.518..427T }}</ref>+ + − XNA also has potential applications to be used as catalysts, much like RNA has the ability to be used as an enzyme. Researchers have shown XNA is able to cleave and ligate DNA, RNA and other XNA sequences, with the most activity being XNA catalyzed reactions on XNA molecules. This research may be used in determining whether DNA and RNA's role in life emerged through natural selection processes or if it was simply a coincidental occurrence. − XNA还可以作催化剂，就像RNA可以当作酶一样。研究人员已经证明，XNA能够剪切和连接DNA、RNA和其他XNA序列，其中XNA对XNA分子的催化反应最具活性。这项研究可以用来确定DNA和RNA在生命中的作用是通过自然选择过程产生的，还是说仅仅是一个巧合。+ + + − XNA may be employed as molecular clamps in [[quantitative real-time polymerase chain reaction]]s (qPCR) by hybridizing with target DNA sequences.<ref name="A novel xenonucleic acid-mediated m">{{cite journal | vauthors = Sun Q, Pastor L, Du J, Powell MJ, Zhang A, Bodmer W, Wu J, Zheng S, Sha MY | display-authors = 6 | title = A novel xenonucleic acid-mediated molecular clamping technology for early colorectal cancer screening | journal = PLOS ONE | volume = 16 | issue = 10 | pages = e0244332 | date = 2021-10-05 | pmid = 34610014 | pmc = 8491914 | doi = 10.1371/journal.pone.0244332 | bibcode = 2021PLoSO..1644332S | doi-access = free }}</ref> In a study published in [[PLOS One|PLOS ONE]], an XNA-mediated molecular clamping assay detected mutant cell-free DNA (cfDNA) from precancerous [[colorectal cancer]] (CRC) lesions and colorectal cancer.<ref name="A novel xenonucleic acid-mediated m"/> XNA may also act as highly specific molecular probes for detection of nucleic acid target sequence.<ref>{{cite journal | vauthors = D'Agata R, Giuffrida MC, Spoto G | title = Peptide Nucleic Acid-Based Biosensors for Cancer Diagnosis | journal = Molecules | volume = 22 | issue = 11 | pages = 1951 | date = November 2017 | pmid = 29137122 | doi = 10.3390/molecules22111951 | pmc = 6150339 | doi-access = free }}</ref> − XNA may be employed as molecular clamps in quantitative real-time polymerase chain reactions (qPCR) by hybridizing with target DNA sequences. In a study published in PLOS ONE, an XNA-mediated molecular clamping assay detected mutant cell-free DNA (cfDNA) from precancerous colorectal cancer (CRC) lesions and colorectal cancer. XNA may also act as highly specific molecular probes for detection of nucleic acid target sequence. − − XNA可以通过与靶DNA序列杂交，作为定量实时聚合酶链式反应（qPCR）的分子钳。在《公共科学图书馆》（PLOS ONE）期刊上发表的一项研究中，一种DNA介导的分子钳技术检测到了癌前结直肠癌 (CRC)病变和结直肠癌的突变无细胞DNA（cfDNA）。XNA还可以作为检测核酸靶序列的高特异性分子探针。 − − == See also == − * [[Nucleic acid analogue]] − * [[Xenobiology]] − − * Nucleic acid analogue − * Xenobiology − − = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = 核酸类似物 异源生物学 − − == References == − {{reflist}} − {{Nucleic acids}} − [[Category:Helices]]+ − + − Category:Helices − Category:Nucleic acids − 类别: 螺旋体类别: 核酸 − <noinclude>+ − <small>This page was moved from [[wikipedia:en:Xeno nucleic acid]]. Its edit history can be viewed at [[XNA/edithistory]]</small></noinclude> − + +
无编辑摘要
{{#seo:
|keywords=螺旋体，核酸，XNA
|description=是人工合成的核酸类似物，具有不同于天然核酸DNA和RNA的糖骨架。
}}
[[File:GNA-T_vs._natural_DNA-T.png|thumb|乙二醇核酸(左)是异种核酸的一个例子，因为它的主干与DNA(右)不同。]]
'''异源核酸 Xeno nucleic acids（XNA）'''是人工合成的核酸类似物，具有不同于天然核酸DNA和RNA的糖骨架。<ref name="Schmidt2012">{{cite book |last=Schmidt|first=Markus | name-list-style = vanc |title=Synthetic Biology |url=https://books.google.com/books?id=lr0SgX1Hx2gC&pg=PA151|access-date=9 May 2013|year= 2012|publisher=John Wiley & Sons|isbn=978-3-527-65926-5|pages=151–}}</ref>截止至2011年，已证明至少有六种合成的糖类能形成可存储和检索基因信息的核酸骨架。目前正在研究用合成的聚合酶来转化XNA。对其生产和应用的研究创造了一个被称为'''异源生物学 xenobiology'''的领域。
虽然遗传信息仍然存储在四个标准碱基对（不像其他核酸类似物那样），但是天然的DNA聚合酶不能读取和复制这些信息。因此，存储在XNA中的遗传信息是“不可视的”，对于以天然DNA为基础的生物体来说是无用的。<ref name="Schmidt1">{{cite journal | vauthors = Schmidt M | title = Xenobiology: a new form of life as the ultimate biosafety tool | journal = BioEssays | volume = 32 | issue = 4 | pages = 322–331 | date = April 2010 | pmid = 20217844 | pmc = 2909387 | doi = 10.1002/bies.200900147 }}</ref>
==背景==
DNA的结构于1953年被发现。大约在21世纪初，研究人员创造了许多奇特的类DNA结构，XNA。XNA是一种人工合成的聚合物，可以携带与DNA相同的信息，但具有不同的分子成分。XNA中的“X”代表“ xeno”，意思是外乡人或外星人，以表示其分子结构与DNA或RNA相比的差异。<ref name=":1" />
在特殊的聚合酶被开发出来之前，对XNA的研究并不多，这种酶能够以DNA为模板复制出XNA，也能将XNA复制回DNA。<ref name=":1">{{Cite web |last=Gonzales |first=Robbie | name-list-style = vanc |title=XNA Is Synthetic DNA That's Stronger than the Real Thing |website=[[Io9]] |date=19 April 2012 |access-date=15 October 2015 |url=http://io9.com/5903221/meet-xna-the-first-synthetic-dna-that-evolves-like-the-real-thing}}</ref>例如Pinheiro等人在2012年的一项研究已证明了一种可以在大约100bp序列长度上工作的XNA聚合酶。<ref name="Synthetic genetic polymers capable">{{cite journal | vauthors = Pinheiro VB, Taylor AI, Cozens C, Abramov M, Renders M, Zhang S, Chaput JC, Wengel J, Peak-Chew SY, McLaughlin SH, Herdewijn P, Holliger P | display-authors = 6 | title = Synthetic genetic polymers capable of heredity and evolution | journal = Science | volume = 336 | issue = 6079 | pages = 341–344 | date = April 2012 | pmid = 22517858 | pmc = 3362463 | doi = 10.1126/science.1217622 | bibcode = 2012Sci...336..341P }}</ref>最近，合成生物学家菲利普·霍利格 Philipp Holliger和亚历山大·泰勒 Alexander Taylor成功地创造了XNAzymes。XNAzymes相当于核酶，由DNA或核糖核酸构成。这表明，这表明XNAs不仅存储遗传信息，还可以作为酶，这提高了其他地方的生命可能起源于RNA或DNA以外物质的可能性。<ref>{{Cite web |website=[[Medical Research Council (United Kingdom)|Medical Research Council]] |title=World's first artificial enzymes created using synthetic biology |date=1 December 2014 |url=http://www.mrc.ac.uk/news/browse/world-s-first-artificial-enzymes-created-using-synthetic-biology/}}</ref>
== Structure 结构 ==
== Structure 结构 ==
[[File:Sugars of DNA and XNA.jpeg|thumb|369x369px|This image displays the differences in the sugar backbones used in XNAs compared to common and biologically used DNA and RNA.|链接=Special:FilePath/Sugars_of_DNA_and_XNA.jpeg]]
[[File:Sugars of DNA and XNA.jpeg|thumb|369x369px|这张图片显示了XNAs中使用的糖主链与普通和生物学上使用的DNA和RNA的区别。]]
这张图片显示了XNAs中使用的糖骨架与生物学中常见的DNA和RNA之间的差异。DNA链和RNA链是由名为核苷酸的长链分子串联而成的。核苷酸由三种化学成分组成：磷酸、五碳糖（可以是脱氧核糖，它给DNA提供了“D”，也可以是核糖，即RNA中的“R”) 、以及五种标准碱基之一（腺嘌呤 adenine、鸟嘌呤 guanine、胞嘧啶 cytosine、胸腺嘧啶 thymine或尿嘧啶 uracil）。
这张图片显示了XNAs中使用的糖骨架与生物学中常见的DNA和RNA之间的差异。DNA链和RNA链是由名为核苷酸的长链分子串联而成的。核苷酸由三种化学成分组成：磷酸、五碳糖（可以是脱氧核糖，它给DNA提供了“D”，也可以是核糖，即RNA中的“R”) 、以及五种标准碱基之一（腺嘌呤、鸟嘌呤、胞嘧啶、胸腺嘧啶或尿嘧啶）。
组成这六种异源核酸的分子与DNA和RNA的分子几乎完全相同，只有一处例外：在XNA核苷酸中，DNA和RNA的脱氧核糖和核糖被其他化学结构所取代。这些替换使得XNAs功能和结构上与DNA和RNA相似，尽管它们是非自然的、人工的。
组成这六种异源核酸的分子与DNA和RNA的分子几乎完全相同，只有一处例外：在XNA核苷酸中，DNA和RNA的脱氧核糖和核糖被其他化学结构所取代。这些替换使得XNAs功能和结构上与DNA和RNA相似，尽管它们是非自然的、人工的。
XNA相对于DNA和RNA能表现出各种结构上的化学变化。迄今为止合成的XNA类型包括: <ref name="Schmidt1" />
XNA相对于DNA和RNA能表现出各种结构上的化学变化。迄今为止合成的XNA类型包括:
* 1,5-脱水己醇核酸（HNA）
* 1,5-脱水己醇核酸（HNA）
* 环己烯核酸（CeNA）
* 环己烯核酸（CeNA）
* 锁核酸（LNA）
* 锁核酸（LNA）
* 肽核酸（PNA）
* 肽核酸（PNA）
* 2氟-阿拉伯糖核酸（FANA）
* 氟阿拉伯核酸（FANA）
HNA可被用作识别和结合特定序列的药物。科学家已经能够分离出HNAs，以靶向结合艾滋病毒相关的基因序列。<ref>{{Cite web |title = Polymers perform non-DNA evolution |url = http://www.rsc.org/chemistryworld/News/2012/April/xna-hna-primordial-life-dna-evolution-chemistry.asp |first=Andy |last=Extance | name-list-style = vanc |date=19 April 2012 |website = [[Royal Society of Chemistry]] |access-date = 15 October 2015}}</ref>研究表明，在存在环己烯核酸的情况下，具有类似D型立体化学结构的CeNAs可以与自身和RNA形成稳定的双链体。结果表明，当CeNAs与DNA形成双链体时，CeNAs不是很稳定。<ref>{{cite journal | vauthors = Gu P, Schepers G, Rozenski J, Van Aerschot A, Herdewijn P | title = Base pairing properties of D- and L-cyclohexene nucleic acids (CeNA) | journal = Oligonucleotides | volume = 13 | issue = 6 | pages = 479–489 | year = 2003 | pmid = 15025914 | doi = 10.1089/154545703322860799 }}</ref>
==启示==
XNA研究的目的不是为了让科学家更好地了解历史上发生过的生物进化，而是探索我们能够控制甚至重新编程生物体基因组成的方法。XNA在解决目前转基因生物的遗传污染问题上显示出巨大潜力。<ref>{{cite journal | vauthors = Herdewijn P, Marlière P | title = Toward safe genetically modified organisms through the chemical diversification of nucleic acids | journal = Chemistry & Biodiversity | volume = 6 | issue = 6 | pages = 791–808 | date = June 2009 | pmid = 19554563 | doi = 10.1002/cbdv.200900083 | s2cid = 8572188 }}</ref>尽管DNA在储存遗传信息和提供复杂生物多样性方面具有令人难以置信的效率，但其四个字母的遗传密码表相对有限。使用6个XNAs的遗传密码而不是4个自然产生的DNA碱基，或将展现出基因修饰和扩展化学功能的无尽机遇。<ref>{{cite journal | vauthors = Pinheiro VB, Holliger P | title = The XNA world: progress towards replication and evolution of synthetic genetic polymers | journal = Current Opinion in Chemical Biology | volume = 16 | issue = 3–4 | pages = 245–252 | date = August 2012 | pmid = 22704981 | doi = 10.1016/j.cbpa.2012.05.198 }}</ref>
关于XNAs的各种假说和理论的发展已经改变了目前我们理解核酸的一个关键点: 遗传和进化并不是人们曾经认为的那样只局限于DNA和RNA，而仅仅是一种起源于能够储存信息的聚合物的简单过程。对于XNAs的研究将允许研究人员评估DNA和RNA是不是最有效和最理想的生命构件，或者这两种分子是不是在更大类的化学祖先进化之后被随机地选择出来的。<ref>{{cite journal | vauthors = Hunter P | title = XNA marks the spot. What can we learn about the origins of life and the treatment of disease through artificial nucleic acids? | journal = EMBO Reports | volume = 14 | issue = 5 | pages = 410–413 | date = May 2013 | pmid = 23579343 | pmc = 3642382 | doi = 10.1038/embor.2013.42 }}</ref>
== 应用 ==
一种利用XNA的理论是将其作为抗病剂纳入医学。目前，一些用于各种疾病治疗的酶和抗体在胃或血液中分解得太快。但由于XNA是外来的，而且人类尚未进化出能够分解它们的酶，因此对于目前正在使用的DNA和RNA治疗方法，XNA可能成为比它们更持久的替换物。<ref name=":0">{{Cite web|title = XNA: Synthetic DNA That Can Evolve|url = http://www.popularmechanics.com/science/health/a7636/xna-synthetic-dna-that-can-evolve-8210483/|website = [[Popular Mechanics]] |date = 19 April 2012 |access-date = 17 November 2015}}</ref>
XNA实验已经可以替换和扩大遗传密码表，而且XNA已经显示出与DNA和RNA核苷酸的互补性，这表明它具有转录和重组的潜力。在佛罗里达大学进行的一项实验中，通过AEISIS-SELEX（人工扩增的遗传信息系统——通过指数富集的配体的系统进化）产生了一种XNA适配体，并成功与乳腺癌细胞系结合。<ref>{{cite journal | vauthors = Sefah K, Yang Z, Bradley KM, Hoshika S, Jiménez E, Zhang L, Zhu G, Shanker S, Yu F, Turek D, Tan W, Benner SA | display-authors = 6 | title = In vitro selection with artificial expanded genetic information systems | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 4 | pages = 1449–1454 | date = January 2014 | pmid = 24379378 | pmc = 3910645 | doi = 10.1073/pnas.1311778111 | doi-access = free | bibcode = 2014PNAS..111.1449S }}</ref>此外，在大肠杆菌中的实验表明，XNA在体内具有作为DNA生物模板的能力。<ref>{{cite journal | vauthors = Pezo V, Liu FW, Abramov M, Froeyen M, Herdewijn P, Marlière P | title = Binary genetic cassettes for selecting XNA-templated DNA synthesis in vivo | journal = Angewandte Chemie | volume = 52 | issue = 31 | pages = 8139–8143 | date = July 2013 | pmid = 23804524 | doi = 10.1002/anie.201303288 | url = https://lirias.kuleuven.be/handle/123456789/413046 }}</ref>
在推进对XNAs的基因研究时，必须考虑到有关生物安全、生物防护、伦理和治理/监管的各种问题。<ref name="Schmidt1" />这里的一个关键问题是，在体内环境中，XNA是否会与自然环境中的DNA和RNA混合，从而使科学家无法控制或预测其在基因突变中可能的影响。<ref name=":0" />
XNA还可以作催化剂，就像RNA可以当作酶一样。研究人员已经证明，XNA能够剪切和连接DNA、RNA和其他XNA序列，其中XNA对XNA分子的催化反应最具活性。这项研究可以用来确定DNA和RNA在生命中的作用是通过自然选择过程产生的，还是说仅仅是一个巧合。<ref>{{cite journal | vauthors = Taylor AI, Pinheiro VB, Smola MJ, Morgunov AS, Peak-Chew S, Cozens C, Weeks KM, Herdewijn P, Holliger P | display-authors = 6 | title = Catalysts from synthetic genetic polymers | journal = Nature | volume = 518 | issue = 7539 | pages = 427–430 | date = February 2015 | pmid = 25470036 | pmc = 4336857 | doi = 10.1038/nature13982 | bibcode = 2015Natur.518..427T }}</ref>
XNA可以通过与靶DNA序列杂交，作为定量实时聚合酶链式反应 quantitative real-time polymerase chain reaction（qPCR）的分子钳。<ref name="A novel xenonucleic acid-mediated m">{{cite journal | vauthors = Sun Q, Pastor L, Du J, Powell MJ, Zhang A, Bodmer W, Wu J, Zheng S, Sha MY | display-authors = 6 | title = A novel xenonucleic acid-mediated molecular clamping technology for early colorectal cancer screening | journal = PLOS ONE | volume = 16 | issue = 10 | pages = e0244332 | date = 2021-10-05 | pmid = 34610014 | pmc = 8491914 | doi = 10.1371/journal.pone.0244332 | bibcode = 2021PLoSO..1644332S | doi-access = free }}</ref>在《公共科学图书馆》（PLOS ONE）期刊上发表的一项研究中，一种DNA介导的分子钳技术检测到了癌前结直肠癌 colorectal cancer(CRC)病变和结直肠癌的突变无细胞DNA cell-free DN（cfDNA）。<ref name="A novel xenonucleic acid-mediated m"/>XNA还可以作为检测核酸靶序列的高特异性分子探针。<ref>{{cite journal | vauthors = D'Agata R, Giuffrida MC, Spoto G | title = Peptide Nucleic Acid-Based Biosensors for Cancer Diagnosis | journal = Molecules | volume = 22 | issue = 11 | pages = 1951 | date = November 2017 | pmid = 29137122 | doi = 10.3390/molecules22111951 | pmc = 6150339 | doi-access = free }}</ref>
== 参见 ==
* [[核酸类似物]]
* [[异源生物学]]
== 参考文献 ==
{{reflist}}
==编者推荐==
===集智课程===
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[[Category:Nucleic acids]]
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