SEARCHNARRATIVE_REVIEWbiomedical research, preclinical research

narrative_review·biomedical research, preclinical research, research methods·PMC10080534

Recent advances in therapeutic CRISPR-Cas9 genome editing: mechanisms and applications

Molecular Biomedicine · 2 authors, 1 centre

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This narrative review describes the mechanisms and therapeutic applications of CRISPR-Cas9 genome editing tools, including base and prime editors.

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This narrative review summarizes the evolution, mechanisms, and therapeutic applications of CRISPR-Cas9 derived genome editing tools. It details how wild-type Cas9 induces double-strand breaks (DSBs) repaired by error-prone non-homologous end joining (NHEJ) for gene disruption or by homology-directed repair (HDR) for precise changes. The review also describes modified Cas9 systems for transcriptional regulation, epigenetic remodeling, base editing, and prime editing.

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narrative_review

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biomedical research

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ORIGINAL PAPER

PMC10080534

Recent advances in therapeutic CRISPR-Cas9 genome editing: mechanisms and applications

Molecular Biomedicine

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ABSTRACT

Recently, clustered regularly interspaced palindromic repeats (CRISPR)-Cas9 derived editing tools had significantly improved our ability to make desired changes in the genome. Wild-type Cas9 protein recognizes the target genomic loci and induced local double strand breaks (DSBs) in the guidance of small RNA molecule. In mammalian cells, the DSBs are mainly repaired by endogenous non-homologous end joining (NHEJ) pathway, which is error prone and results in the formation of indels. The indels can be harnessed to interrupt gene coding sequences or regulation elements. The DSBs can also be fixed by homology directed repair (HDR) pathway to introduce desired changes, such as base substitution and fragment insertion, when proper donor templates are provided, albeit in a less efficient manner. Besides making DSBs, Cas9 protein can be mutated to serve as a DNA binding platform to recruit functional modulators to the target loci, performing local transcriptional regulation, epigenetic remolding, base editing or prime editing. These Cas9 derived editing tools, especially base editors and prime editors, can introduce precise changes into the target loci at a single-base resolution and in an efficient and irreversible manner. Such features make these editing tools very promising for therapeutic applications. This review focuses on the evolution and mechanisms of CRISPR-Cas9 derived editing tools and their applications in the field of gene therapy.

CITATION EXPORT

Lifang Zhou, Shaohua Yao. Recent advances in therapeutic CRISPR-Cas9 genome editing: mechanisms and applications. Molecular Biomedicine. (2023). https://doi.org/10.1186/s43556-023-00115-5

AUTHORS

2 · 1 CENTRES

Lifang Zhou, Shaohua Yao

grid.412901.f0000 0004 1770 1022Laboratory of Biotherapy, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Renmin Nanlu 17, Chengdu, 610041 Sichuan China