提高精确的 CRISPR/Cas9 介导的基因组编辑的方法。
Approaches to Enhance Precise CRISPR/Cas9-Mediated Genome Editing.
机构信息
The Dr. John and Anne Chong Lab for Functional Genomics, Charles Perkins Centre and School of Life & Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
Centenary Institute, The University of Sydney, Sydney, NSW 2006, Australia.
出版信息
Int J Mol Sci. 2021 Aug 9;22(16):8571. doi: 10.3390/ijms22168571.
Modification of the human genome has immense potential for preventing or treating disease. Modern genome editing techniques based on CRISPR/Cas9 show great promise for altering disease-relevant genes. The efficacy of precision editing at CRISPR/Cas9-induced double-strand breaks is dependent on the relative activities of nuclear DNA repair pathways, including the homology-directed repair and error-prone non-homologous end-joining pathways. The competition between multiple DNA repair pathways generates mosaic and/or therapeutically undesirable editing outcomes. Importantly, genetic models have validated key DNA repair pathways as druggable targets for increasing editing efficacy. In this review, we highlight approaches that can be used to achieve the desired genome modification, including the latest progress using small molecule modulators and engineered CRISPR/Cas proteins to enhance precision editing.
人类基因组的修饰在预防或治疗疾病方面具有巨大的潜力。基于 CRISPR/Cas9 的现代基因组编辑技术在改变与疾病相关的基因方面显示出巨大的潜力。CRISPR/Cas9 诱导的双链断裂的精确编辑的功效取决于核 DNA 修复途径的相对活性，包括同源定向修复和易错非同源末端连接途径。多种 DNA 修复途径之间的竞争会产生嵌合体和/或治疗上不理想的编辑结果。重要的是，遗传模型已经验证了关键的 DNA 修复途径作为提高编辑效率的可药物靶点。在这篇综述中，我们强调了可以用来实现所需的基因组修饰的方法，包括使用小分子调节剂和工程化的 CRISPR/Cas 蛋白来增强精确编辑的最新进展。
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