title: A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae.
abstract: Gene drive systems that enable super-Mendelian inheritance of a transgene have the potential to modify insect populations over a timeframe of a few years. We describe CRISPR-Cas9 endonuclease constructs that function as gene drive systems in Anopheles gambiae, the main vector for malaria. We identified three genes (AGAP005958, AGAP011377 and AGAP007280) that confer a recessive female-sterility phenotype upon disruption, and inserted into each locus CRISPR-Cas9 gene drive constructs designed to target and edit each gene. For each targeted locus we observed a strong gene drive at the molecular level, with transmission rates to progeny of 91.4 to 99.6%. Population modeling and cage experiments indicate that a CRISPR-Cas9 construct targeting one of these loci, AGAP007280, meets the minimum requirement for a gene drive targeting female reproduction in an insect population. These findings could expedite the development of gene drives to suppress mosquito populations to levels that do not support malaria transmission.
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hammond
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Roberto
authors.identifier: http://orcid.org/0000-0003-3134-7480
authors.initials: R
authors.lastname: Galizi
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Kyros
authors.initials: K
authors.lastname: Kyrou
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Alekos
authors.initials: A
authors.lastname: Simoni
authors.affiliation: Dipartimento di Medicina Sperimentale Via Gambuli, Centro di Genomica Funzionale, University of Perugia, Perugia, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Siniscalchi
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Katsanos
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Gribble
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge, UK.
authors.forename: Dean
authors.initials: D
authors.lastname: Baker
authors.affiliation: INSERM U963, CNRS UPR9022, Université de Strasbourg, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Marois
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge, UK.
authors.forename: Steven
authors.initials: S
authors.lastname: Russell
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Austin
authors.initials: A
authors.lastname: Burt
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Nikolai
authors.identifier: http://orcid.org/0000-0001-9896-1165
authors.initials: N
authors.lastname: Windbichler
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Crisanti
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Tony
authors.initials: T
authors.lastname: Nolan
mesh_terms: D000818:Animals; D000852:Anopheles / Q000235:genetics / Q000502:physiology*; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D005260:Female; D007303:Insect Vectors; D008288:Malaria / Q000635:transmission*