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Mathematical modeling of self-contained CRISPR gene drive reversal systems. | LitMetric

Mathematical modeling of self-contained CRISPR gene drive reversal systems.

Sci Rep

Department of Biochemistry and Molecular Biophysics, 141 Chalmers Hall, Kansas State University, Manhattan, KS 66506, USA.

Published: December 2019

AI Article Synopsis

  • There's a pressing need for research on controlling biological populations to address challenges in agriculture, ecology, and human health by managing pests and disease vectors.
  • The CRISPR/Cas gene editing technology has transformed how genetic elements can be manipulated in entire populations, offering methods to alter species without following traditional inheritance patterns.
  • Current studies are exploring gene drive systems that can "program" changes during propagation, potentially allowing for controlled reversals to restore original populations, addressing concerns about the unintended consequences of these technologies.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934693PMC
http://dx.doi.org/10.1038/s41598-019-54805-8DOI Listing

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