Homing endonuclease mediated gene targeting in Anopheles gambiae cells and embryos

Nikolai Windbichler, Philippos Aris Papathanos, Flaminia Catteruccia, Hilary Ranson, Austin Burt, Andrea Crisanti*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

Homing endonuclease genes (HEGs) are 'selfish' genetic elements that combine the capability to selectively disrupt specific gene sequences with the ability to rapidly spread from a few individuals to an entire population through homologous recombination repair events. Because of these properties, HEGs are regarded as promising candidates to transfer genetic modifications from engineered laboratory mosquitoes to wild-type populations including Anopheles gambiae the vector of human malaria. Here we show that I-SceI and I-PpoI homing endonucleases cleave their recognition sites with high efficiency in A. gambiae cells and embryos and we demonstrate HEG-induced homologous and non-homologous repair events in a variety of functional assays. We also propose a gene drive system for mosquitoes that is based on our finding that I-PpoI cuts genomic rDNA located on the X chromosome in A. gambiae, which could be used to selectively incapacitate X-carrying spermatozoa thereby imposing a severe male-biased sex ratio.

Original languageAmerican English
Pages (from-to)5922-5933
Number of pages12
JournalNucleic Acids Research
Volume35
Issue number17
DOIs
StatePublished - Sep 2007
Externally publishedYes

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