Implementing and Modeling Gene Drives for Population Modification and Suppression

Author: Ivy, Tobin William

Year: 2024

Degree: Dissertation (Ph.D.)

Advisor: Hay, Bruce A.

Committee Members: Sternberg, Paul W.; Elowitz, Michael B.; Bois, Justin S.; Hay, Bruce A.

Option: Biochemistry and Molecular Biophysics

Abstract

Gene drive as a technology has immense potential for modifying species from the local to the global population level. While the advent of the CRISPR-Cas9 system has paved the way for many previously untenable gene drives, it has also illuminated two substantial pitfalls: homing based gene drives are particularly susceptible to generating drive breaking resistance alleles and many if not most gene drives are too powerful to be regionally contained. Lack of confinability makes such gene drives impractical for real world application where international law would be violated by their usage. We developed a new general form of gene drive known as cleave and rescue (ClvR), then built and simulated the potential of multiple variants of this drive which are capable of modifying or suppressing target populations, including variants with and without introduction thresholds for drive. We also developed scripts in Python capable of generating population dynamics simulations of a user-defined gene drive, either as a deterministic, population proportion model or a stochastic, discrete individual model. This tool provides a very useful first pass answer about a given gene drive’s ability to modify or suppress a population under varying fitness costs, drive activity rates, and release proportions.