Engineering a self-eliminating transgene in the yellow fever mosquito, Aedes aegypti.
PNAS Nexus
; 1(2): pgac037, 2022 May.
Article
em En
| MEDLINE
| ID: mdl-36713320
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.
Texto completo:
1
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article