Engineering a self-eliminating transgene in the yellow fever mosquito, Aedes aegypti. Academic Article uri icon

abstract

  • Promising genetics-based approaches are being developed to reduce or prevent the transmission of mosquito-vectored diseases. Less clear is how such transgenes can be removed from the environment, a concern that is particularly relevant for highly invasive gene drive transgenes. Here, we lay the groundwork for a transgene removal system based on single-strand annealing (SSA), a eukaryotic DNA repair mechanism. An SSA-based rescuer strain (kmoRG ) was engineered to have direct repeat sequences (DRs) in the Aedes aegypti kynurenine 3-monooxygenase (kmo) gene flanking the intervening transgenic cargo genes, DsRED and EGFP. Targeted induction of DNA double-strand breaks (DSBs) in the DsRED transgene successfully triggered complete elimination of the entire cargo from the kmoRG strain, restoring the wild-type kmo gene, and thereby, normal eye pigmentation. Our work establishes the framework for strategies to remove transgene sequences during the evaluation and testing of modified strains for genetics-based mosquito control.

published proceedings

  • PNAS Nexus

altmetric score

  • 97.25

author list (cited authors)

  • Chae, K., Dawson, C., Valentin, C., Contreras, B., Zapletal, J., Myles, K. M., & Adelman, Z. N.

citation count

  • 4

complete list of authors

  • Chae, Keun||Dawson, Chanell||Valentin, Collin||Contreras, Bryan||Zapletal, Josef||Myles, Kevin M||Adelman, Zach N

editor list (cited editors)

  • Nelson, K. E.

publication date

  • May 2022