Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, United States; Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
Joan Chung
Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, United States; Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
Yoo Lim Lee
Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, United States; Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
Chen Liu
Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, United States; Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
Emily Yang
Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, United States; Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
Zhaoxin Wen
Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, United States
Andrew G Clark
Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, United States
CRISPR-based homing gene drives have sparked both enthusiasm and deep concerns due to their potential for genetically altering entire species. This raises the question about our ability to prevent the unintended spread of such drives from the laboratory into a natural population. Here, we experimentally demonstrate the suitability of synthetic target site drives as well as split drives as flexible safeguarding strategies for gene drive experiments by showing that their performance closely resembles that of standard homing drives in Drosophila melanogaster. Using our split drive system, we further find that maternal deposition of both Cas9 and gRNA is required to form resistance alleles in the early embryo and that maternally-deposited Cas9 alone can power germline drive conversion in individuals that lack a genomic source of Cas9.
