Theoretical Exploration of the Feasibility, Challenges and Risks of Synthetic Gene Drives – TheoGeneDrive

Genetic control with gene drives consists in biasing genetic inheritance in sexually reproducing organisms. With the development of CRISPR-Cas9 gene editing tools, population control with synthetic gene drives has recently become a realistic possibility. The technique has far ranging potential applications, including the control of agricultural pests, of insect vectors of infectious diseases, or of invasive populations, and represents a promising alternative to pesticides. Proof of concept studies in controlled settings have confirmed that a trait, even if deleterious, can spread in a population thanks to the self-replicating properties of a CRISPR-Cas9 construct. Gene drives thus have the potential to permanently alter wild populations. Yet, more is currently known about the molecular biology of synthetic gene drives than their ecological and evolutionary impacts on populations and their ecosystems. This project aims at filling this gap, by using mathematical and computational eco-evolutionary models. First, we will assess the feasibility of gene drives for the modification or eradication of wild populations in realistic settings: What is the probability that a gene drive construct establishes in a population? Can it spread spatially even when designed for population eradication? How do specificities of the target species’ life-cycle affect the spread of gene drives? Second, we will evaluate the evolutionary challenges that gene drives will face: how and how fast will resistance evolve? Can a gene drive trigger the evolution of life-cycle features that will feed back on its spread? Third, we will investigate the environmental risks, ethical and regulatory issues associated to the technique: What are the impacts on ecosystems? Can we control a rogue gene drive? What are the societal, ethical and regulatory implications of gene drives, and how can we address them? Our results will be instrumental to developing an interdisciplinary and independent expertise in France and in the European Union on this promising but controversial new technology.