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bioRxiv · 10.1101/2024.05.14.594116

A Y chromosome-linked genome editor for efficient population suppression in the malaria vector Anopheles gambiae

Tolosana, I.·Willis, K.·Burt, A.·Gribble, M.·Nolan, T.·Crisanti, A.·Bernardini, F.
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Abstract

Genetic control - the deliberate introduction of genetic traits to control a pest or vector population - offers a powerful tool to augment conventional mosquito control tools that have been successful in reducing malaria burden but that are compromised by a range of operational challenges. Self-sustaining genetic control strategies have shown great potential in laboratory settings but hesitancy due to their invasive and persistent nature may delay their implementation. Here instead we describe a self-limiting strategy, designed to have geographically and/or temporally restricted effect, based on a Y chromosome-linked genome editor (YLE). The YLE comprises a CRISPR-Cas9 construct that is always inherited by males yet generates an autosomal dominant mutation that is transmitted to over 90% of the offspring and results in female-specific sterility. Males are unaffected. To our knowledge, our system represents the first engineering of the Y chromosome to generate a genetic control strain for mosquitoes. Mathematical modelling shows that this YLE technology is up to 8 times more efficient for population suppression than optimal versions of other self-limiting strategies.

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Tolosana, I., Willis, K., Burt, A., Gribble, M., Nolan, T., Crisanti, A., Bernardini, F.. 2024-05-14. A Y chromosome-linked genome editor for efficient population suppression in the malaria vector Anopheles gambiae. https://doi.org/10.1101/2024.05.14.594116

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