Cas12f1 gene drives propagate efficiently in herpesviruses and induce minimal resistance.

Autor: Lin Z; Department of Immunology, School of Basic Medicine, Southern Medical University, Guangzhou, Guangdong Province, China., Yao Q; Department of Immunology, School of Basic Medicine, Southern Medical University, Guangzhou, Guangdong Province, China., Lai K; Department of Immunology, School of Basic Medicine, Southern Medical University, Guangzhou, Guangdong Province, China., Jiao K; Department of Geriatric Medicine, Shanghai Health and Medical Center, Wuxi, Jiangshu Province, China., Zeng X; Department of Immunology, School of Basic Medicine, Southern Medical University, Guangzhou, Guangdong Province, China., Lei G; Affiliated Hospital of Xiangnan University, Chenzhou, Hunan Province, China.; Key Laboratory of Medical Imaging and Artificial Intelligence of Hunan Province, Chenzhou, Hunan Province, China., Zhang T; Department of Immunology, School of Basic Medicine, Southern Medical University, Guangzhou, Guangdong Province, China. vaccine-sz@outlook.com.; Vaccine Biotech (Shenzhen) LTD, Shenzhen, China, & Boji Biopharmaceutical, Guangzhou, China. vaccine-sz@outlook.com., Dai H; Department of Immunology, School of Basic Medicine, Southern Medical University, Guangzhou, Guangdong Province, China. daihsh@outlook.com.
Jazyk: angličtina
Zdroj: Genome biology [Genome Biol] 2024 Dec 18; Vol. 25 (1), pp. 311. Date of Electronic Publication: 2024 Dec 18.
DOI: 10.1186/s13059-024-03455-9
Abstrakt: Background: Synthetic CRISPR-Cas9 gene drive has been developed to control harmful species. However, resistance to Cas9 gene drive can be acquired easily when DNA repair mechanisms patch up the genetic insults introduced by Cas9 and incorporate mutations to the sgRNA target. Although many strategies to reduce the occurrence of resistance have been developed so far, they are difficult to implement and not always effective.
Results: Here, Cas12f1, a recently developed CRISPR-Cas system with minimal potential for causing mutations within target sequences, has been explored as a potential platform for yielding low-resistance in gene drives. We construct Cas9 and Cas12f1 gene drives in a fast-replicating DNA virus, HSV1. Cas9 and Cas12f1 gene drives are able to spread among the HSV1 population with specificity towards their target sites, and their transmission among HSV1 viruses is not significantly affected by the reduced fitness incurred by the viral carriers. Cas12f1 gene drives spread similarly as Cas9 gene drives at high introduction frequency but transmit more slowly than Cas9 gene drives at low introduction frequency. However, Cas12f1 gene drives outperform Cas9 gene drives because they reach higher penetration and induce lower resistance than Cas9 gene drives in all cases.
Conclusions: Due to lower resistance and higher penetration, Cas12f1 gene drives could potentially supplant Cas9 gene drives for population control.
Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: Tongwen Zhang is currently an employee of Boji Biopharmaceutical. The authors declare no competing interests. Neither their employers nor the funding agency had any influence on the study design, data collection, analysis, or interpretation of results.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: