基因编辑之“新宠”—单碱基基因组编辑系统

发布时间：2018-09-11 19:30

【摘要】：近年发展起来的人工核酸酶可通过引起特定位点的DNA双链断裂实现对目的片段的有效编辑。为进一步提高碱基修改的效率和精确度,2016年研究者们利用CRISPR/Cas9识别特定DNA序列的功能,结合胞嘧啶脱氨酶的生化活性发明了将胞嘧啶高效转换为胸腺嘧啶(CT)的嘧啶单碱基编辑系统(base editor)。这一系统虽然能精准实现嘧啶直接转换,大大提高精确基因编辑效率,但美中不足的是无法对嘌呤进行修改。近期,Nature报道了将细菌中的t RNA腺嘌呤脱氨酶定向进化形成具有催化DNA腺嘌呤底物的脱氨酶,将其与Cas9系统融合发明了具有高效催化腺嘌呤转换为鸟嘌呤的新工具—腺嘌呤单碱基编辑系统(ABEs,adenine base editors)。本文总结了单碱基编辑工具的发展历程和最新研究进展,着重介绍ABEs的研发过程,并对单碱基编辑工具今后的应用方向和研发方向进行展望。
[Abstract]:The artificial nucleases developed in recent years can effectively edit the target fragments by causing DNA double strand breaks at specific sites. To further improve the efficiency and accuracy of base modifications, researchers used CRISPR/Cas9 to identify specific DNA sequences in 2016. Combined with the biochemical activity of cytosine deaminase, a pyrimidine single base editing system (base editor).) was developed to efficiently convert cytosine to thymine (CT). Although this system can accurately realize direct conversion of pyrimidine and greatly improve the efficiency of accurate gene editing, the deficiency of this system is that the purine cannot be modified. Recently, it was reported that t RNA adenine deaminase in bacteria evolved into a deaminase that catalyzes DNA adenine substrate. Combining it with Cas9 system, a new tool which can catalyze the conversion of adenine to guanine, adenine single base editing system (ABEs,adenine base editors).) has been developed. This paper summarizes the development history and the latest research progress of the single base editing tool, emphatically introduces the research and development process of ABEs, and looks forward to the future application and research direction of the single base editing tool.
【作者单位】：上海市调控生物学重点实验室华东师范大学生命科学学院;
【基金】：国家自然科学基金项目(编号:81670470)资助~~
【分类号】：Q78

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