Genetic conversion of a split-drive into a full-drive element

• DOI: 10.1038/s41467-022-35044-4
• Publication Date: 2023-01-12T16:05:50Z
• Authors: Gerard Terradas; Jared B. Bennett; Zhiqian Li; John M. Marshall; Ethan Bier
• Keywords: Guide RNA; Gene drive

The core components of CRISPR-based gene drives, Cas9 and guide RNA (gRNA), either can be linked within a self-contained single cassette (full gene-drive, fGD) or provided in two separate elements (split sGD), the latter offering greater control options. We previously engineered split systems that could converted genetically into autonomous full drives. Here, we examine such dual inserted at spo11 locus are recoded to restore function thus organismic fertility. Despite minimal differences transmission efficiency sGD fGD drive generation crosses, reconstituted surprisingly exhibits slower initial kinetics than unlinked element multigenerational cage studies, but then eventually catches up achieve similar level final introduction. These unexpected kinetic behaviors most likely reflect differing transient fitness costs associated with individuals co-inheriting gRNA transgenes during process.