Small-Molecule Control of Super-Mendelian Inheritance in Gene Drives.

Cell Rep
Authors
Abstract

Synthetic CRISPR-based gene-drive systems have tremendous potential in public health and agriculture, such as for fighting vector-borne diseases or suppressing crop pest populations. These elements can rapidly spread in a population by breaching the inheritance limit of 50% dictated by Mendel's law of gene segregation, making them a promising tool for population engineering. However, current technologies lack control over their propagation capacity, and there are important concerns about potential unchecked spreading. Here, we describe a gene-drive system in Drosophila that generates an analog inheritance output that can be tightly and conditionally controlled to between 50% and 100%. This technology uses a modified SpCas9 that responds to a synthetic, orally available small molecule, fine-tuning the inheritance probability. This system opens a new avenue to feasibility studies for spatial and temporal control of gene drives using small molecules.

Year of Publication
2020
Journal
Cell Rep
Volume
31
Issue
13
Pages
107841
Date Published
2020 Jun 30
ISSN
2211-1247
DOI
10.1016/j.celrep.2020.107841
PubMed ID
32610142
Links
Grant list
DP5 OD023098 / OD / NIH HHS / United States
R01 GM132825 / GM / NIGMS NIH HHS / United States