{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:40:17Z","timestamp":1791409217982,"version":"4.3.3"},"update-to":[{"DOI":"10.1371\/journal.pgen.1010244","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T00:00:00Z","timestamp":1655164800000}}],"reference-count":82,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1158151"],"award-info":[{"award-number":["OPP1158151"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1158151"],"award-info":[{"award-number":["OPP1158151"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Gene drives for mosquito population modification are novel tools for malaria control. Strategies to safely test antimalarial effectors in the field are required. Here, we modified the <jats:italic>Anopheles gambiae zpg<\/jats:italic> locus to host a CRISPR\/Cas9 integral gene drive allele (<jats:italic>zpg<\/jats:italic><jats:sup><jats:italic>D<\/jats:italic><\/jats:sup>) and characterized its behaviour and resistance profile. We found that <jats:italic>zpg<\/jats:italic><jats:sup><jats:italic>D<\/jats:italic><\/jats:sup> dominantly sterilizes females but can induce efficient drive at other loci when it itself encounters resistance. We combined <jats:italic>zpg<\/jats:italic><jats:sup><jats:italic>D<\/jats:italic><\/jats:sup> with multiple previously characterized non-autonomous payload drives and found that, as <jats:italic>zpg<\/jats:italic><jats:sup><jats:italic>D<\/jats:italic><\/jats:sup> self-eliminates, it leads to conversion of mosquito cage populations at these loci. Our results demonstrate how self-eliminating drivers could allow safe testing of non-autonomous effector-traits by local population modification. They also suggest that after engendering resistance, gene drives intended for population suppression could nevertheless serve to propagate subsequently released non-autonomous payload genes, allowing modification of vector populations initially targeted for suppression.<\/jats:p>","DOI":"10.1371\/journal.pgen.1010244","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T17:45:45Z","timestamp":1654191945000},"page":"e1010244","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":30,"title":["Testing non-autonomous antimalarial gene drive effectors using self-eliminating drivers in the African mosquito vector Anopheles gambiae"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3366-7712","authenticated-orcid":true,"given":"David A.","family":"Ellis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5489-2003","authenticated-orcid":true,"given":"George","family":"Avraam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1346-5945","authenticated-orcid":true,"given":"Astrid","family":"Hoermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0449-8507","authenticated-orcid":true,"given":"Claudia A. S.","family":"Wyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3134-2236","authenticated-orcid":true,"given":"Yi Xin","family":"Ong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3323-1687","authenticated-orcid":true,"given":"George K.","family":"Christophides","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9896-1165","authenticated-orcid":true,"given":"Nikolai","family":"Windbichler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"pgen.1010244.ref001","article-title":"WHO World Malaria Report 2020","author":"World Health Organization","year":"2020","journal-title":"Malaria report"},{"key":"pgen.1010244.ref002","article-title":"Site-specific selfish genes as tools for the control and genetic engineering of natural populations","author":"A. 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Forks Enables Multiplex Genome Engineering in Eukaryotes","author":"EM Barbieri","year":"2017","journal-title":"Cell"},{"key":"pgen.1010244.ref045","article-title":"Multiplex genome engineering using CRISPR\/Cas systems","author":"L Cong","year":"2013","journal-title":"Science (80-)"},{"key":"pgen.1010244.ref046","article-title":"Multiplexed CRISPR technologies for gene editing and transcriptional regulation","author":"NS McCarty","year":"2020","journal-title":"Nat Commun"},{"key":"pgen.1010244.ref047","article-title":"Versatile transgenic multistage effector-gene combinations for Plasmodium falciparum suppression in Anopheles","author":"Y Dong","year":"2020","journal-title":"Sci Adv."},{"key":"pgen.1010244.ref048","article-title":"Evolutionary biology and genetic techniques for insect control","author":"PT Leftwich","year":"2015"},{"key":"pgen.1010244.ref049","article-title":"Transcription regulation of sex-biased genes during ontogeny in the Malaria vector Anopheles gambiae","author":"K Magnusson","year":"2011","journal-title":"PLoS One"},{"key":"pgen.1010244.ref050","article-title":"Genetic diversity of the African malaria vector anopheles gambiae","author":"A Miles","year":"2017","journal-title":"Nature"},{"key":"pgen.1010244.ref051","article-title":"Recombinant scorpine: A multifunctional antimicrobial peptide with activity against different pathogens","author":"R Carballar-Lejaraz\u00fa","year":"2008","journal-title":"Cell Mol Life Sci"},{"key":"pgen.1010244.ref052","article-title":"Spermless males elicit large-scale female responses to mating in the malaria mosquito Anopheles gambiae","author":"J Thailayil","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pgen.1010244.ref053","article-title":"Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics","author":"PA Eckhoff","year":"2017","journal-title":"Proc Natl Acad Sci U S 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Bier","year":"2021","journal-title":"Nat Rev Genet"},{"key":"pgen.1010244.ref055","article-title":"High cleavage efficiency of a 2A peptide derived from porcine teschovirus-1 in human cell lines, zebrafish and mice","author":"JH Kim","year":"2011","journal-title":"PLoS One"},{"key":"pgen.1010244.ref056","article-title":"Systematic comparison of 2A peptides for cloning multi-genes in a polycistronic vector","author":"Z Liu","year":"2017","journal-title":"Sci Rep"},{"key":"pgen.1010244.ref057","doi-asserted-by":"crossref","first-page":"9013","DOI":"10.1073\/pnas.1921698117","article-title":"Gene drive and resilience through renewal with next generation Cleave and Rescue selfish genetic elements","volume":"117","author":"G Oberhofer","journal-title":"Proc Natl Acad Sci U S A."},{"key":"pgen.1010244.ref058","first-page":"246","article-title":"Active Genetic Neutralizing Elements for Halting or Deleting Gene Drives","volume":"80","author":"XS Xu","journal-title":"Mol Cell"},{"key":"pgen.1010244.ref059","article-title":"Rapid induction by a blood meal of a carboxypeptidase gene in the gut of the mosquito Anopheles gambiae","author":"MJ Edwards","year":"1997","journal-title":"Insect Biochem Mol Biol"},{"key":"pgen.1010244.ref060","article-title":"Molecular analysis of the Aedes aegypti carboxypeptidase gene family","author":"J Isoe","year":"2009","journal-title":"Insect Biochem Mol Biol"},{"key":"pgen.1010244.ref061","first-page":"11","article-title":"Invasion and migration of spatially self-limiting gene drives: A comparative analysis","author":"S Dhole","year":"2018","journal-title":"Evol Appl"},{"key":"pgen.1010244.ref062","first-page":"8","article-title":"A reduce and replace strategy for suppressing vector-borne diseases: Insights from a stochastic, spatial model","author":"KW Okamoto","year":"2013","journal-title":"PLoS One"},{"key":"pgen.1010244.ref063","first-page":"8","article-title":"A Reduce and Replace Strategy for Suppressing Vector-Borne Diseases: Insights from a Deterministic Model","author":"MA Robert","year":"2013","journal-title":"PLoS One"},{"key":"pgen.1010244.ref064","first-page":"7","article-title":"Current CRISPR gene drive systems are likely to be highly invasive in wild populations","author":"C Noble","year":"2018","journal-title":"Elife"},{"key":"pgen.1010244.ref065","first-page":"9","article-title":"Locally Fixed Alleles: A method to localize gene drive to island populations","author":"J Sudweeks","year":"2019","journal-title":"Sci Rep"},{"key":"pgen.1010244.ref066","article-title":"Computational and experimental performance of CRISPR homing gene drive strategies with multiplexed gRNAs","author":"SE Champer","year":"2020","journal-title":"Sci Adv"},{"key":"pgen.1010244.ref067","article-title":"Next-generation gene drive for population modification of the malaria vector mosquito, Anopheles gambiae","author":"R Carballar-Lejaraz\u00fa","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pgen.1010244.ref068","article-title":"Experimental population modification of the malaria vector mosquito, Anopheles stephensi","author":"TB Pham","year":"2019","journal-title":"PLoS Genet."},{"key":"pgen.1010244.ref069","article-title":"A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae","author":"A Simoni","year":"2020","journal-title":"Nat Biotechnol"},{"key":"pgen.1010244.ref070","article-title":"Gene drive for population genetic control: Non-functional resistance and parental effects","author":"AK Beaghton","year":"2019","journal-title":"Proc R Soc B Biol Sci"},{"key":"pgen.1010244.ref071","article-title":"Overcoming evolved resistance to population-suppressing homing-based gene drives","author":"JM Marshall","year":"2017","journal-title":"Sci Rep"},{"key":"pgen.1010244.ref072","article-title":"VectorBase: An updated Bioinformatics Resource for invertebrate vectors and other organisms related with human diseases","author":"GI Giraldo-Calder\u00f3n","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"pgen.1010244.ref073","article-title":"New connections between splicing and human disease","author":"RA Padgett","year":"2012","journal-title":"Trends Genet"},{"key":"pgen.1010244.ref074","article-title":"A synthetic sex ratio distortion system for the control of the human malaria mosquito","author":"R Galizi","year":"2014","journal-title":"Nat Commun"},{"key":"pgen.1010244.ref075","article-title":"MScarlet: A bright monomeric red fluorescent protein for cellular imaging","author":"DS Bindels","year":"2016","journal-title":"Nat Methods"},{"key":"pgen.1010244.ref076","article-title":"Mosquito transgenic technologies to reduce plasmodium transmission","author":"S Fuchs","year":"2013","journal-title":"Methods Mol Biol"},{"key":"pgen.1010244.ref077","article-title":"Tools for anopheles gambiae transgenesis","author":"G Volohonsky","year":"2015","journal-title":"G3 Genes. 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