TY - JOUR T1 - Efficient allelic-drive in Drosophila. JF - Nat Commun Y1 - 2019 A1 - Guichard, Annabel A1 - Haque, Tisha A1 - Bobik, Marketta A1 - Xu, Xiang-Ru S A1 - Klanseck, Carissa A1 - Kushwah, Raja Babu Singh A1 - Berni, Mateus A1 - Kaduskar, Bhagyashree A1 - Gantz, Valentino M A1 - Bier, Ethan KW - Agriculture KW - Alleles KW - Animals KW - Animals, Genetically Modified KW - CRISPR-Cas Systems KW - DNA End-Joining Repair KW - DNA Mutational Analysis KW - Drosophila KW - Female KW - Gene Drive Technology KW - Gene Editing KW - Inheritance Patterns KW - Male KW - Mosaicism KW - RNA, Guide AB -

Gene-drive systems developed in several organisms result in super-Mendelian inheritance of transgenic insertions. Here, we generalize this "active genetic" approach to preferentially transmit allelic variants (allelic-drive) resulting from only a single or a few nucleotide alterations. We test two configurations for allelic-drive: one, copy-cutting, in which a non-preferred allele is selectively targeted for Cas9/guide RNA (gRNA) cleavage, and a more general approach, copy-grafting, that permits selective inheritance of a desired allele located in close proximity to the gRNA cut site. We also characterize a phenomenon we refer to as lethal-mosaicism that dominantly eliminates NHEJ-induced mutations and favors inheritance of functional cleavage-resistant alleles. These two efficient allelic-drive methods, enhanced by lethal mosaicism and a trans-generational drive process we refer to as "shadow-drive", have broad practical applications in improving health and agriculture and greatly extend the active genetics toolbox.

VL - 10 IS - 1 ER -