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. 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. Due to lower resistance and higher penetration, Cas12f1 gene drives could potentially supplant Cas9 gene drives for population control.

Zhuangjie Lin

Qiaorui Yao

Keyuan Lai

Kehua Jiao

Xianying Zeng

Guanxiong Lei

Tongwen Zhang

Hongsheng Dai

Genome biology

基因组生物学涵盖从基因组和后基因组角度研究的生物学和生物医学的所有领域。内容包括研究、新方法和软件工具，以及评论、意见和评论。涵盖的领域包括但不限于：序列分析；生物信息学；深入了解分子、细胞和有机体生物学；功能基因组学；表观基因组学；群体基因组学；蛋白质组学；比较生物学和进化论；系统和网络生物学；基因组编辑和工程；疾病基因组学；和临床基因组学。

Genome Biology covers all areas of biology and biomedicine studied from the perspectives of genomics and post-genomics. The content includes research articles, new methods and software tools, as well as reviews and opinions. The fields covered include, but are not limited to: sequence analysis; bioinformatics; in-depth studies of molecular, cellular, and organismal biology; functional genomics; epigenomics; population genomics; proteomics; comparative biology and evolution; systems and network biology; genome editing and engineering; disease genomics; and clinical genomics.

《Genome Biology》期刊涵盖了从基因组和后基因组的角度研究生物学和生物医学的各个领域。内容包括研究论文、新方法和软件工具，以及评论和意见。涉及的领域包括但不限于：序列分析、生物信息学、分子、细胞和有机体生物学的深入研究、功能基因组学、表观基因组学、群体基因组学、蛋白质组学、比较生物学和进化论、系统和网络生物学、基因组编辑和工程、疾病基因组学以及临床基因组学。

Cas12f1 gene drives propagate efficiently in herpesviruses and induce minimal resistance

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Journal Info

Category	Quartile
GENETICS & HEREDITY	1