Homology-based repair induced by CRISPR-Cas nucleases in mammalian embryo genome editing

Recent advances in genome editing,especially CRISPR-Cas nucleases,have revolutionized both laboratory research and clinical therapeutics.CRISPR-Cas nucleases,together with the DNA damage repair pathway in cells,enable both genetic diversification by classical non-homologous end joining(c-NHEJ)and precise genome modification by homology-based repair(HBR).Genome editing in zygotes is a convenient way to edit the germline,paving the way for animal disease model generation,as well as human embryo genome editing therapy for some life-threatening and incurable diseases.HBR efficiency is highly dependent on the DNA donor that is utilized as a repair template.Here,we review recent progress in improving CRISPR-Cas nuclease-induced HBR in mammalian embryos by designing a suitable DNA donor.Moreover,we want to provide a guide for producing animal disease models and correcting genetic mutations through CRISPR-Cas nuclease-induced HBR in mammalian embryos.Finally,we discuss recent developments in precise genome-modification technology based on the CRISPR-Cas system.