Viruses that ‘infect’ viruses: Cas12f1 and Cas9 gene drive in HSV1

Hongsheng Dai, Qiaorui Yao, Zhuangjie Lin, Keyuan Lai, Xianyin Zeng, Guangxiong Lei, Tongwen Zhang,  bioRxiv,  2023.

Cas9-based synthetic gene drives constitute some minimal elements capable of editing DNA with sequence specificity. However, they face high resistance rate and mitigation strategies developed so far are difficult to implement. Here, we engineered herpes simplex virus type 1 (HSV1) as a vector for gene drive, generated viruses carrying either Cas9 or Cas12f1 gene drives, and compared their performance in spreading the gene drive and causing resistance. Based on phenotypical staining and NGS sequencing, we showed that HSV1 supported fast and effective transmission of gene drive, and Cas12f1 gene drive yielded higher conversion and lower resistance than Cas9 gene drive. Cas12f1 gene drive is a promising alternative to Cas9 gene drive, and HSV1 is a reliable and fast platform to evaluate gene drive. Gene drive viruses worked like pathogens that specifically infect viruses and could potentially be used to attenuate viral infection.

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