Development of zygotic and germline gene drives in mice

CRISPR-based synthetic gene drives have the potential to deliver a more effective and humane method of invasive vertebrate pest control than current strategies. Relatively efficient CRISPR gene drives have been developed in insects and yeast but not in mammals. Here we investigated the efficiency of CRISPR/Cas9-based gene drives in Mus musculus by constructing "split drive" systems with Cas9 under the control of zygotic (CAG) or germline (Vasa) promoters. While both systems generated double stranded breaks at their intended target site in vivo, no homing was detectable. Our data indicate that robust and specific Cas9 expression during meiosis is a critical requirement for the generation of efficient CRISPR-based synthetic gene drives in rodents.