Citation: Gong Shaohua, Li Na, Tang Bo. Recent Progress in Regulating CRISPR-Cas9 System for Gene Editing[J]. Acta Chimica Sinica, ;2020, 78(7): 634-641. doi: 10.6023/A20040131 shu

Recent Progress in Regulating CRISPR-Cas9 System for Gene Editing

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, China

Corresponding author: Li Na, lina@sdnu.edu.cn
Received Date: 29 April 2020
Available Online: 8 June 2020
Fund Project: the National Natural Science Foundation of China 21775094the National Key R & D Program of China 2019YFA0210100the National Natural Science Foundation of China 21535004the Youth Innovation Science and Technology Program of Higher Education Institution of Shandong Province 2019KJC022the Key Research and Development Program of Shandong Province 2018YFJH0502Project supported by the National Key R & D Program of China (No. 2019YFA0210100), the National Natural Science Foundation of China (Nos. 21535004, 91753111, 21927881, 21874086, 21775094), the Key Research and Development Program of Shandong Province (No. 2018YFJH0502), and the Youth Innovation Science and Technology Program of Higher Education Institution of Shandong Province (No. 2019KJC022)the National Natural Science Foundation of China 21927881the National Natural Science Foundation of China 21874086the National Natural Science Foundation of China 91753111

Figures(8)

Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) system is an adaptive immune system used by many bacteria and archaea to defend the invasion of exogenous nucleic acids. CRISPR-Cas system in different species of archaea and bacteria has different components and working mechanisms. Depending on the numbers of effector proteins, CRISPR-Cas systems can be classified into two major types. CRISPR-Cas9, which is composed of Cas9 nuclease and sgRNA, belongs to class Ⅱ CRISPR-Cas system and can be used as a powerful genome editing tool. It can target and cleave the DNA sequence which contains protospacer adjacent motif (PAM, 5'-NGG-3') sequence. The DNA double-strand breaks (DSBs) can be repaired by homology-directed repair (HDR) or nonhomologous end joining (NHEJ) mechanism. Insertions or deletions (indels) can be introduced at targeted loci in the DSBs repair process. Due to its convenience, low cost and high efficiency, CRISPR-Cas9 has played an important role in promoting the development of gene editing in basic research and clinical medicine. However, off-target effect of CRISPR-Cas9 should not be neglected. The CRISPR-Cas9 is able to cleave the target DNA even when the sgRNA imperfectly matches with the target DNA, leading to the unwanted indels at nontargeted DNA loci, which limits the further application of genome editing, especially for the treatment of genetic diseases. Therefore, it is significant to reduce the off-target cleavage effect of CRISPR-Cas9. Many efforts have been devoted to realize the reduced off-target effect of CRISPR-Cas9. Among these methods, regulating the function of CRISPR-Cas9 at spatiotemporal dimension is a potential strategy to reduce the off-target effect of CRISPR-Cas9 system and improve the specificity of gene editing. In this review, we summarized the research advances in regulating the function of CRISPR-Cas9 and discussed the prospects and challenges of CRISPR-Cas9 regulation.
- CRISPR-Cas9,
- gene editing,
- specificity,
- off-target effect,
- regulation
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沈阳化工大学材料科学与工程学院沈阳 110142