人类遗传病致病基因一半以上是点突变，对其进行精确、高效的原位修复是遗传病治疗最理想的方式。鉴于点突变中大部分为鸟嘌呤(G)与腺嘌呤(A)之间的转换，而基于CRISPR/Cas9(clustered regularly interspaced short palindromic repeats-Cas9)系统的腺嘌呤碱基编辑器(adenine base editor，ABE)通过将A转换为G，从而修复这些突变，因此该种碱基编辑在人类遗传病治疗中特别重要。近年来，ABE不断被优化，特别是碱基编辑器的活性和保真性均被提高。本文总结了有关ABE的研究进展，特别是ABE研发过程中重要的突变体，同时对现有ABE仍然存在的缺陷进行了思考。另外，对ABE在临床(含临床前研究)方面的相关应用也进行了回顾。本文为发现和优化新型ABE及其应用提供参考。
Adenine Base Editor and Its Clinical Application
The mutations in human disease-causing genes are predominantly caused by point mutations,with more than half of them being transitions between guanine(G)and adenine(A).Precise and efficient in situ repair of these mutations is the most ideal approach for the treatment of genetic diseases.Given that most point mutations are transitions between G and A,adenine base editors(ABEs)based on the CRISPR/Cas9 system,which convert A to G,are particularly important for repairing these mutations in the treatment of human genetic diseases.In recent years,ABEs have been continuously optimized,with both activity and fidelity being improved.Here we summarize the progress of ABEs,especially those key mutants developed during the process of ABE optimization.It also reflects on the existing defects in current ABEs.Additionally,the article reviews the clinical applications(including preclinical studies)of ABE.Overall,the article aims to provide references for the discovery and optimization of new ABEs and their applications.
adenine base editorgene therapyCRISPR/Cas9 technology
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维普
