Strategies for In Vivo Genome Editing in Nondividing Cells

Programmable nucleases, including zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9), have enhanced our ability to edit genomes by the sequence-specific generation of double-strand breaks (DSBs) with subsequent homology-directed repair (HDR) of the DSB. However, the efficiency of the HDR pathway is limited in nondividing cells, which encompass most of the cells in the body. Therefore, the HDR-mediated genome-editing approach has limited in vivo applicability. Here, we discuss a mutation type-oriented viewpoint of strategies devised over the past few years to circumvent this problem, along with their possible applications and limitations.