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

Nat Commun. 2025 Jan 2;16(1):206. doi: 10.1038/s41467-024-55391-8.

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 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. To our knowledge, our system represents a pioneering approach in the engineering of the Y chromosome to generate a genetic control strain for mosquitoes. Mathematical modelling shows that this YLE technology is up to seven times more efficient for population suppression than optimal versions of other self-limiting strategies, such as the widely used Sterile Insect Technique or the Release of Insects carrying a Dominant Lethal gene.

MeSH terms

  • Animals
  • Anopheles* / genetics
  • CRISPR-Cas Systems*
  • Female
  • Gene Editing* / methods
  • Genome, Insect
  • Malaria* / prevention & control
  • Malaria* / transmission
  • Male
  • Mosquito Control* / methods
  • Mosquito Vectors* / genetics
  • Y Chromosome* / genetics