Un1Cas12f1 and Cas9 gene drive in HSV1: viruses that ‘infect’ viruses

Cas9-based synthetic gene drives have been used for pest control, however, they face high resistance rates, and mitigation strategies developed thus far are difficult to implement. Here, we engineered herpes simplex virus type 1 (HSV1) as a vector for gene drive, generated viruses harboring either the Cas9 or Un1Cas12f1 gene drive, and evaluated these viruses for spreading gene drive and causing resistance. HSV1 supported fast and effective transmission of gene drives, and the Un1Cas12f1 gene drives yielded greater conversion and lower resistance than did the Cas9 gene drives. This positions the Un1Cas12f1 gene drive as a promising alternative, and HSV1 emerges as a dependable and swift platform for gene drive assessment. The gene drive viruses function like pathogens that specifically infect viruses, offering potential applications in attenuating viral infections.