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

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

Cell Reports (Jun 2020)

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

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

Affiliations

Víctor López Del Amo: Section of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA
Brittany S. Leger: Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
Kurt J. Cox: Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Divisions of Renal Medicine and Engineering, Brigham and Women’s Hospital, Boston, MA 02115, USA
Shubhroz Gill: Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Alena L. Bishop: Section of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA
Garrett D. Scanlon: Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
James A. Walker: Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Corresponding author
Valentino M. Gantz: Section of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA; Corresponding author
Amit Choudhary: Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Divisions of Renal Medicine and Engineering, Brigham and Women’s Hospital, Boston, MA 02115, USA; Corresponding author

Journal volume & issue: Vol. 31, no. 13
p. 107841

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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