Recent advances in therapeutic CRISPR-Cas9 genome editing: mechanisms and applications
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 guid...
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| Format: | Article |
| Language: | English |
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Springer
2023-04-01
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| Series: | Molecular Biomedicine |
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| Online Access: | https://doi.org/10.1186/s43556-023-00115-5 |
| _version_ | 1797850218504388608 |
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| author | Lifang Zhou Shaohua Yao |
| author_facet | Lifang Zhou Shaohua Yao |
| author_sort | Lifang Zhou |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T18:56:50Z |
| format | Article |
| id | doaj.art-2c6bd1f421c54b44ae527d9d02903e72 |
| institution | Directory Open Access Journal |
| issn | 2662-8651 |
| language | English |
| last_indexed | 2024-04-09T18:56:50Z |
| publishDate | 2023-04-01 |
| publisher | Springer |
| record_format | Article |
| series | Molecular Biomedicine |
| spelling | doaj.art-2c6bd1f421c54b44ae527d9d02903e722023-04-09T11:06:21ZengSpringerMolecular Biomedicine2662-86512023-04-014112510.1186/s43556-023-00115-5Recent advances in therapeutic CRISPR-Cas9 genome editing: mechanisms and applicationsLifang Zhou0Shaohua Yao1Laboratory of Biotherapy, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan UniversityLaboratory of Biotherapy, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan UniversityAbstract 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. https://doi.org/10.1186/s43556-023-00115-5CRISPR/Cas9Base editingPrime editingGene therapyGene Delivery |
| spellingShingle | Lifang Zhou Shaohua Yao Recent advances in therapeutic CRISPR-Cas9 genome editing: mechanisms and applications Molecular Biomedicine CRISPR/Cas9 Base editing Prime editing Gene therapy Gene Delivery |
| title | Recent advances in therapeutic CRISPR-Cas9 genome editing: mechanisms and applications |
| title_full | Recent advances in therapeutic CRISPR-Cas9 genome editing: mechanisms and applications |
| title_fullStr | Recent advances in therapeutic CRISPR-Cas9 genome editing: mechanisms and applications |
| title_full_unstemmed | Recent advances in therapeutic CRISPR-Cas9 genome editing: mechanisms and applications |
| title_short | Recent advances in therapeutic CRISPR-Cas9 genome editing: mechanisms and applications |
| title_sort | recent advances in therapeutic crispr cas9 genome editing mechanisms and applications |
| topic | CRISPR/Cas9 Base editing Prime editing Gene therapy Gene Delivery |
| url | https://doi.org/10.1186/s43556-023-00115-5 |
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