López Del Amo, V., Leger, B.S., Cox, K.J., Gill, S., Bishop, A.L., Scanlon, G.D., Walker, J.A., Gantz, V.M., Choudhary, A. (2020). Small-Molecule Control of Super-Mendelian Inheritance in Gene Drives. Cell Rep. 31(13): 107841.
FlyBase ID
FBrf0246061
Publication Type
Research paper
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.
