Department of Biotechnology
inStem (Institute for Stem Cell Science and Regenerative Medicine)

Efficient allelic-drive in Drosophila.

Publication Type

Research Support, Non-U.S. Gov't

Date of Publication

April 9, 2019

Journal

Nature communications

Volume/Issue

10/1

ISSN

2041-1723

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.

Alternate Journal

Nat Commun

PubMed ID

30967548

PubMed Central ID

PMC6456580

Authors

Annabel Guichard
Tisha Haque
Marketta Bobik
Xiang-Ru S Xu
Carissa Klanseck
Raja Babu Singh Kushwah
Mateus Berni
Bhagyashree Kaduskar
Valentino M Gantz
Ethan Bier

Keywords

Mosaicism
RNA, Guide, CRISPR-Cas Systems
Agriculture
Animals
Alleles
Drosophila
Animals, Genetically Modified
DNA End-Joining Repair
Female
DNA Mutational Analysis
Male
Gene Drive Technology
CRISPR-Cas Systems
Inheritance Patterns
Gene Editing