Small-Molecule Control of Super-Mendelian Inheritance in Gene Drives
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 Mend...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-06-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720308226 |
| _version_ | 1818970667140251648 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Víctor López Del Amo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T14:40:07Z |
| format | Article |
| id | doaj.art-df15ab12cf9c4df997f1b386eee938d8 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-20T14:40:07Z |
| publishDate | 2020-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-df15ab12cf9c4df997f1b386eee938d82022-12-21T19:37:21ZengElsevierCell Reports2211-12472020-06-013113107841Small-Molecule Control of Super-Mendelian Inheritance in Gene DrivesVíctor López Del Amo0Brittany S. Leger1Kurt J. Cox2Shubhroz Gill3Alena L. Bishop4Garrett D. Scanlon5James A. Walker6Valentino M. Gantz7Amit Choudhary8Section of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USACenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USAChemical 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, USAChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USASection of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USACenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USACenter 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 authorSection of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA; Corresponding authorChemical 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124720308226gene drivesplit gene driveCopyCatsuper-Mendeliansmall moleculedrug control |
| spellingShingle | 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 Small-Molecule Control of Super-Mendelian Inheritance in Gene Drives Cell Reports gene drive split gene drive CopyCat super-Mendelian small molecule drug control |
| title | Small-Molecule Control of Super-Mendelian Inheritance in Gene Drives |
| title_full | Small-Molecule Control of Super-Mendelian Inheritance in Gene Drives |
| title_fullStr | Small-Molecule Control of Super-Mendelian Inheritance in Gene Drives |
| title_full_unstemmed | Small-Molecule Control of Super-Mendelian Inheritance in Gene Drives |
| title_short | Small-Molecule Control of Super-Mendelian Inheritance in Gene Drives |
| title_sort | small molecule control of super mendelian inheritance in gene drives |
| topic | gene drive split gene drive CopyCat super-Mendelian small molecule drug control |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720308226 |
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