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通过核酸的化学多样化实现安全的转基因生物。

Toward safe genetically modified organisms through the chemical diversification of nucleic acids.

作者信息

Herdewijn Piet, Marlière Philippe

机构信息

Laboratory for Medicinal Chemistry, Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven.

出版信息

Chem Biodivers. 2009 Jun;6(6):791-808. doi: 10.1002/cbdv.200900083.

Abstract

It is argued that genetic proliferation should be rationally extended so as to enable the propagation in vivo of additional types of nucleic acids (XNA for 'xeno-nucleic acids'), whose chemical backbone motifs would differ from deoxyribose and ribose, and whose polymerization would not interfere with DNA and RNA biosynthesis. Because XNA building blocks do not occur in nature, they would have to be synthesized and supplied to cells which would be equipped with an appropriate enzymatic machinery for polymerizing them. The invasion of plants and animals with XNA replicons can be envisioned in the long run, but it is in microorganisms, and more specifically in bacteria, that the feasibility of such chemical systems and the establishment of genetic enclaves separated from DNA and RNA is more likely to take place. The introduction of expanded coding through additional or alternative pairing will be facilitated by the propagation of replicons based on alternative backbone motifs and leaving groups, as enabled by XNA polymerases purposefully evolved to this end.

摘要

有人认为,基因增殖应合理扩展,以便能够在体内繁殖其他类型的核酸(“异种核酸”的XNA),其化学主链基序将不同于脱氧核糖和核糖,并且其聚合不会干扰DNA和RNA的生物合成。由于XNA构建块在自然界中不存在,因此必须合成并提供给配备有适当聚合酶机制的细胞。从长远来看,可以设想用XNA复制子侵入植物和动物,但在微生物中,更具体地说是在细菌中,这种化学系统的可行性以及与DNA和RNA分离的基因飞地的建立更有可能发生。通过基于替代主链基序和离去基团的复制子的繁殖,将促进通过额外或替代配对引入扩展编码,这是为此目的而有目的地进化的XNA聚合酶所实现的。

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