Journal
G3-GENES GENOMES GENETICS
Volume 8, Issue 3, Pages 999-1018Publisher
GENETICS SOCIETY AMERICA
DOI: 10.1534/g3.117.300557
Keywords
CRISPR; Cas9; budding yeast; gene drive; sgRNA; regulating gene drives; biotechnology
Categories
Funding
- Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health [P20 GM103418]
- USDA National Institute of Food and Agriculture, Hatch Project [1013520]
- Johnson Cancer Research Center at Kansas State University
- College of Arts and Sciences at Kansas State University
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P20GM103418] Funding Source: NIH RePORTER
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Control of biological populations is an ongoing challenge in many fields, including agriculture, biodiversity, ecological preservation, pest control, and the spread of disease. In some cases, such as insects that harbor human pathogens (e.g., malaria), elimination or reduction of a small number of species would have a dramatic impact across the globe. Given the recent discovery and development of the CRISPR-Cas9 gene editing technology, a unique arrangement of this system, a nuclease-based gene drive, allows for the super-Mendelian spread and forced propagation of a genetic element through a population. Recent studies have demonstrated the ability of a gene drive to rapidly spread within and nearly eliminate insect populations in a laboratory setting. While there are still ongoing technical challenges to design of a more optimal gene drive to be used in wild populations, there are still serious ecological and ethical concerns surrounding the nature of this powerful biological agent. Here, we use budding yeast as a safe and fully contained model system to explore mechanisms that might allow for programmed regulation of gene drive activity. We describe four conserved features of all CRISPR-based drives and demonstrate the ability of each drive componentCas9 protein level, sgRNA identity, Cas9 nucleocytoplasmic shuttling, and novel Cas9-Cas9 tandem fusionsto modulate drive activity within a population.
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