Gene Drive to Trigger a Population Collapse in Invasive Species

Research Overview

Bruce A. Hay

Georg Oberhofer

Professor Bruce Hay and postdoctoral scholar Georg Oberhofer, along with graduate student Tobin Ivy, have been working to develop ways to suppress populations of invasive species, such as Drosophila Suzukii, an invasive fruit fly that attacks soft fruits and arrived in North America in 2008. They developed a system, called "Cleave and Rescue," to create a genetic addiction to a temperature sensitive version of an essential gene. By using gene drive, a genetic engineering technique to propagate specific genes throughout a population, they pushed this modified gene into a model drosophila species in the lab, and then demonstrated that rising temperatures caused the population to crash. The results, published in the Proceedings of the National Academy of Sciences, show that such techniques could be used to halt the spread of invasive species. You can read the details in the paper, Gene drive that results in addiction to a temperature-sensitive version of an essential gene triggers population collapse in Drosophila.

Scientific Achievement

We demonstrate the replacement of a fly population with a temperature-dependent Cleave and Rescue (ClvR) drive element, followed by suppression of the population as the temperature is changed.

Significance and Impact

This work shows the potential use of a ClvR gene drive platform for species-specific pest/vector elimination.

A) ClvR mechanism of action: Cas9/gRNAs inactivate an essential gene. Those carrying ClvR survive because they also carry an uncleavable Rescue transgene. Here the Rescue is designed to be temperature sensitive through inclusion of an intein that can only be removed at low temperature. B) TS-ClvR flies (red) are released during a low temperature season, replacing the wildtype population. When the temperature increases in summer, the TS-Rescue becomes non-functional and the population collapses. C) Population drive experiment in which TS-ClvR (solid lines) but not a control strain (dotted lines) replaces wildtype within 10 generations at 23C. D) TS-ClvR bearing populations rapidly crash when incubated at 29C. Copyright PNAS 2021.

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A) ClvR mechanism of action: Cas9/gRNAs inactivate an essential gene. Those carrying ClvR survive because they also carry an uncleavable Rescue transgene. Here the Rescue is designed to be temperature sensitive through inclusion of an intein that can only be removed at low temperature. B) TS-ClvR flies (red) are released during a low temperature season, replacing the wildtype population. When the temperature increases in summer, the TS-Rescue becomes non-functional and the population collapses. C) Population drive experiment in which TS-ClvR (solid lines) but not a control strain (dotted lines) replaces wildtype within 10 generations at 23C. D) TS-ClvR bearing populations rapidly crash when incubated at 29C. Copyright PNAS 2021.

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Technical Details

• ClvR uses gene editing tools to disrupt an essential gene, while also including a temperature-dependent Rescue version of the gene. As ClvR spreads, the survival of the population becomes temperature-dependent.
• We built a ClvR (TS-ClvR) in Drosophila in which Rescue activity requires removal of a temperature-sensitive intein. TS-ClvR  spreads to transgene fixation at 23^oC, but when populations now dependent on the Rescue are shifted to 29^oC, the population dies out. 

Oberhofer G, Ivy T, Hay BA., Gene drive that results in addiction to a temperature-sensitive version of an essential gene triggers a population collapse in Drosophila, Proc Natl Acad Sci 2021 118 (49) e2107413118. https://www.pnas.org/content/118/49/e2107413118

Contact: Bruce Hay