TY - JOUR T1 - Genetic conversion of a split-drive into a full-drive element JF - bioRxiv DO - 10.1101/2021.12.05.471291 SP - 2021.12.05.471291 AU - Gerard Terradas AU - Jared B. Bennett AU - Zhiqian Li AU - John M. Marshall AU - Ethan Bier Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/12/06/2021.12.05.471291.abstract N2 - Gene-drive systems offer an important new avenue for spreading beneficial traits into wild populations. Their core components, Cas9 and guide RNA (gRNA), can either be linked within a single cassette (full gene drive, fGD) or provided in two separate elements (split gene drive, sGD) wherein the gRNA-bearing element drives in the presence of an independent static source of Cas9. We previously designed a system engineered to turn split into full gene drives. Here, we provide experimental proof-of-principle for such a convertible system inserted at the spo11 locus, which is recoded to restore gene function. In multigenerational cage studies, the reconstituted spo11 fGD cassette initially drives with slower kinetics than the unlinked sGD element (using the same Mendelian vasa-Cas9 source), but eventually reaches a similar level of final introgression. Different kinetic behaviors may result from transient fitness costs associated with individuals co-inheriting Cas9 and gRNA transgenes during the drive process.Competing Interest StatementE.B. has equity interests in Agragene Inc. and Synbal Inc., companies that may potentially benefit from the research results. E.B. also serves on the company's Board of Directors (Synbal) and Scientific Advisory Board (Synbal and Agragene). The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies. All other authors declare no competing interests. ER -