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

• Main Authors: Víctor López Del Amo, Brittany S. Leger, Kurt J. Cox, Shubhroz Gill, Alena L. Bishop, Garrett D. Scanlon, James A. Walker, Valentino M. Gantz, Amit Choudhary
• Format: Article
• Language: English
• Published: Elsevier 2020-06-01
• Series: Cell Reports
• Subjects: gene drive; split gene drive; CopyCat; super-Mendelian; small molecule; drug control
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124720308226

Summary: 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.