Off-target effects in CRISPR/Cas9 gene editing

Congting Guo; Xiaoteng Ma; Fei Gao; Yuxuan Guo

doi:10.3389/fbioe.2023.1143157

Off-target effects in CRISPR/Cas9 gene editing

Front Bioeng Biotechnol. 2023 Mar 9:11:1143157. doi: 10.3389/fbioe.2023.1143157. eCollection 2023.

Authors

Congting Guo^{1

2}, Xiaoteng Ma³, Fei Gao³, Yuxuan Guo^{1

2

4

5}

Affiliations

¹ School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
² Peking University Institute of Cardiovascular Sciences, Beijing, China.
³ Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
⁴ Ministry of Education Key Laboratory of Molecular Cardiovascular Science, Beijing, China.
⁵ Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, China.

Abstract

Gene editing stands for the methods to precisely make changes to a specific nucleic acid sequence. With the recent development of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, gene editing has become efficient, convenient and programmable, leading to promising translational studies and clinical trials for both genetic and non-genetic diseases. A major concern in the applications of the CRISPR/Cas9 system is about its off-target effects, namely the deposition of unexpected, unwanted, or even adverse alterations to the genome. To date, many methods have been developed to nominate or detect the off-target sites of CRISPR/Cas9, which laid the basis for the successful upgrades of CRISPR/Cas9 derivatives with enhanced precision. In this review, we summarize these technological advancements and discuss about the current challenges in the management of off-target effects for future gene therapy.

Keywords: CRISPR/Cas9; Cas9/sgRNA complex; gene editing; gene therapy; off-target effects.

Publication types

Review

Grants and funding

This work was funded by the National Key R&D Program of China (2022YFA1104800), the National Natural Science Foundation of China (82222006, 32100660, 82170367, 82100349 and 82200405), Beijing Nova Program (Z211100002121003 and 20220484205) and the Postdoctoral Science Foundation of China (2021M692253).