%0 Journal Article %J Nat Commun %D 2019 %T Efficient allelic-drive in Drosophila. %A Guichard, Annabel %A Haque, Tisha %A Bobik, Marketta %A Xu, Xiang-Ru S %A Klanseck, Carissa %A Kushwah, Raja Babu Singh %A Berni, Mateus %A Kaduskar, Bhagyashree %A Gantz, Valentino M %A Bier, Ethan %K Agriculture %K Alleles %K Animals %K Animals, Genetically Modified %K CRISPR-Cas Systems %K DNA End-Joining Repair %K DNA Mutational Analysis %K Drosophila %K Female %K Gene Drive Technology %K Gene Editing %K Inheritance Patterns %K Male %K Mosaicism %K RNA, Guide %X

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.

%B Nat Commun %V 10 %P 1640 %8 2019 04 09 %G eng %N 1 %R 10.1038/s41467-019-09694-w