There is a critical need for further research into methods to control biological populations. Numerous challenges to agriculture, ecological systems, and human health could be mitigated by the targeted reduction and management of key species (e.g. pests, parasites, and vectors for pathogens). The discovery and adaptation of the CRISPR/Cas editing platform co-opted from bacteria has provided a mechanism for a means to alter an entire population. A CRISPR-based gene drive system can allow for the forced propagation of a genetic element that bypasses Mendelian inheritance which can be used to bias sex determination, install exogenous information, or remove endogenous DNA within an entire species. Laboratory studies have demonstrated the potency by which gene drives can operate within insects and other organisms. However, continued research and eventual application face serious opposition regarding issues of policy, biosafety, effectiveness, and reversal. Previous mathematical work has suggested the use of modified gene drive designs that are limited in spread such as daisy chain or underdominance drives. However, no system has yet been proposed that allows for an inducible reversal mechanism without requiring the introduction of additional individuals. Here, we study gene drive effectiveness, fitness, and inducible drive systems that could respond to external stimuli expanding from a previous frequency-based population model. We find that programmed modification during gene drive propagation could serve as a potent safeguard to either slow or completely reverse drive systems and allow for a return to the original wild-type population.
Conflict of interest statement
G.C.F. has applied for CRISPR-related patents: (i) April 20, 2017 by the Univ. of California, Berkeley, “Methods and Compositions for Genomic Editing” International Application No. PCT/US2017/028676 and published as No. WO 2017/189336 A1 on November 2, 2017, (ii) September 29, 2017 (U.S. Provisional Patent Application Serial No. 62/565,651, “Programmed modulation of CRISPR/Cas9 activity”) followed by patent filing on January 31, 2018 and (iii) a PCT application “Multi-Locus Gene Drive System” No. PCT/US2019/041538 on July 12, 2019. M.G.H. has private investments in companies that may utilize various CRISPR-related biotechnologies. Authors declare no non-financial conflict of interest of any kind.
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