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作为脊柱修饰的人造遗传聚合物的甲基核酸

Chao Liu¹, Christopher Cozens², Faten Jaziri³

¹Medicinal Chemistry , Rega Institute for Medical Research, KU Leuven , Herestraat 49 , 3000 Leuven , Belgium.

Journal of the American Chemical Society

|May 4, 2018

概括

研究人员开发了一种新型合成遗传物质,3'-2'甲基-三核酸 (tPhoNA),由于其与天然DNA的正交性,它对体内应用具有前景. 这种新型XNA是在生物体内创造人工遗传系统的重要一步.

科学领域:

合成生物学
生物化学
分子生物学

背景情况:

异生物核酸 (XNA) 显示出作为遗传材料的潜力,但在体内应用中面临挑战,主要是由于缺乏正交性.
正交性要求XNA与天然核酸或酶不相互作用,反之亦然,与专门的XNA处理酶一起.

研究的目的:

报告一种新型的XNA,3-2甲基-三核酸 (tPhoNA),作为体内遗传材料应用的候选物.
证明tPhoNA作为遗传材料的合成和可行性,评估其与酶过程的正交性和兼容性.

主要方法:

酸核酸和化单体构件的化学合成.
在tPhoNA结合时证明DNA双重破坏稳定.
一个新的tPhoNA合成酶的工程和XNA逆转录酶的利用.
在大肠杆菌中进行直角性试验.

主要成果:

已确定的tPhoNA及其构成部分的化学合成途径.
显示tPhoNA会破坏DNA复合的稳定性.
证明tPhoNA是一种可行的遗传材料,总误差率为每基约17 × 10−3,与功能XNA隔离相容.
大肠杆菌细胞机械与tPhoNA遗传信息的有限相互作用得到证实.

结论:

3-2 甲基-三核酸 (tPhoNA) 是一种新型的XNA,具有改性糖和酸盐骨干,代表了生物角性的显著进步.
tPhoNA对体内应用具有前景,它显示了合成遗传系统的基本特征.
这项工作为在体内引入XNA系统铺平了道路,扩大了遗传材料的可能性,超越了自然DNA和RNA.

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