The origin of unwanted editing byproducts in gene editing  

作　　者：Jianhang Yin Jiazhi Hu 

机构地区：[1]The MOE Key Laboratory of Cell Proliferation and Differentiation,School of Life Sciences,Center for Life Sciences,Genome Editing Research Center,Peking University,Beijing 100871,China

出　　处：《Acta Biochimica et Biophysica Sinica》2022年第6期767-781,共15页生物化学与生物物理学报（英文版）

基　　金：the grants from the National Key R&D Program of China(No.,2017YFA0506700);the National Natural Science Fundition of China(Nos.,32122018,31771485);the SLS-Qidong Innovation Fund;the PKU-TSU Center for Life Sciences.

摘　　要：The rapid development of CRISPR-Cas genome editing tools has greatly changed the way to conduct research and holds tremendous promise for clinical applications. During genome editing, CRISPR-Cas enzymes induce DNA breaks at the target sites and subsequently the DNA repair pathways are recruited to generate diverse editing outcomes. Besides off-target cleavage, unwanted editing outcomes including chromosomal structural variations and exogenous DNA integrations have recently raised concerns for clinical safety. To eliminate these unwanted editing byproducts, we need to explore the underlying mechanisms for the formation of diverse editing outcomes from the perspective of DNA repair. Here, we describe the involved DNA repair pathways in sealing Cas enzyme-induced DNA double-stranded breaks and discuss the origins and effects of unwanted editing byproducts on genome stability. Furthermore, we propose the potential risk of inhibiting DNA repair pathways to enhance gene editing. The recent combined studies of DNA repair and CRISPR-Cas editing provide a framework for further optimizing genome editing to enhance editing safety.

关 键 词：genome editing and CRISPR/Cas DSB repair chromosomal translocation large deletion vector DNA integration PEM-seq 

分 类 号：Q5[生物学—生物化学]