{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:41:16Z","timestamp":1791409276186,"version":"4.3.3"},"update-to":[{"DOI":"10.1371\/journal.pgen.1011226","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000}}],"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T00:00:00Z","timestamp":1712275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32072496; 32272571"],"award-info":[{"award-number":["32072496; 32272571"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LZ24C140003"],"award-info":[{"award-number":["LZ24C140003"]}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>CRISPR-based gene drives offer promising prospects for controlling disease-transmitting vectors and agricultural pests. A significant challenge for successful suppression-type drive is the rapid evolution of resistance alleles. One approach to mitigate the development of resistance involves targeting functionally constrained regions using multiple gRNAs. In this study, we constructed a 3-gRNA homing gene drive system targeting the recessive female fertility gene <jats:italic>Tyrosine decarboxylase 2<\/jats:italic> (<jats:italic>Tdc2<\/jats:italic>) in <jats:italic>Drosophila suzukii<\/jats:italic>, a notorious fruit pest. Our investigation revealed only a low level of homing in the germline, but feeding octopamine restored the egg-laying defects in <jats:italic>Tdc2<\/jats:italic> mutant females, allowing easier line maintenance than for other suppression drive targets. We tested the effectiveness of a similar system in <jats:italic>Drosophila melanogaster<\/jats:italic> and constructed additional split drive systems by introducing promoter-Cas9 transgenes to improve homing efficiency. Our findings show that genetic polymorphisms in wild populations may limit the spread of gene drive alleles, and the position effect profoundly influences Cas9 activity. Furthermore, this study highlights the potential of conditionally rescuing the female infertility caused by the gene drive, offering a valuable tool for the industrial-scale production of gene drive transgenic insects.<\/jats:p>","DOI":"10.1371\/journal.pgen.1011226","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T16:29:56Z","timestamp":1712334596000},"page":"e1011226","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["A small-molecule approach to restore female sterility phenotype targeted by a homing suppression gene drive in the fruit pest Drosophila suzukii"],"prefix":"10.1371","volume":"20","author":[{"given":"Suhan","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4781-5747","authenticated-orcid":true,"given":"Xuyang","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9025-093X","authenticated-orcid":true,"given":"Shimin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9590-1319","authenticated-orcid":true,"given":"Xiaomu","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7543-5592","authenticated-orcid":true,"given":"Xuejiao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weizhe","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3814-3774","authenticated-orcid":true,"given":"Jackson","family":"Champer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8336-1562","authenticated-orcid":true,"given":"Jia","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,4,5]]},"reference":[{"key":"pgen.1011226.ref001","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1146\/annurev-biophys-062215-010822","article-title":"CRISPR-Cas9 Structures and Mechanisms","volume":"46","author":"F Jiang","year":"2017","journal-title":"Annu Rev Biophys"},{"issue":"11","key":"pgen.1011226.ref002","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1038\/nbt.4245","article-title":"A CRISPR-Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes","volume":"36","author":"K Kyrou","year":"2018","journal-title":"Nat Biotechnol"},{"issue":"7","key":"pgen.1011226.ref003","doi-asserted-by":"crossref","first-page":"e1006796","DOI":"10.1371\/journal.pgen.1006796","article-title":"Novel CRISPR\/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations","volume":"13","author":"J Champer","year":"2017","journal-title":"Plos Genet"},{"issue":"10","key":"pgen.1011226.ref004","doi-asserted-by":"crossref","first-page":"e1007039","DOI":"10.1371\/journal.pgen.1007039","article-title":"The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito","volume":"13","author":"AM Hammond","year":"2017","journal-title":"Plos Genet"},{"issue":"11","key":"pgen.1011226.ref005","doi-asserted-by":"crossref","first-page":"7461","DOI":"10.1093\/nar\/gku387","article-title":"Development of synthetic selfish elements based on modular nucleases in Drosophila melanogaster","volume":"42","author":"A Simoni","year":"2014","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pgen.1011226.ref006","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/nbt.3439","article-title":"A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae","volume":"34","author":"A Hammond","year":"2016","journal-title":"Nat Biotechnol"},{"issue":"49","key":"pgen.1011226.ref007","doi-asserted-by":"crossref","first-page":"E6736","DOI":"10.1073\/pnas.1521077112","article-title":"Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi","volume":"112","author":"VM Gantz","year":"2015","journal-title":"P Natl Acad Sci Usa"},{"issue":"5","key":"pgen.1011226.ref008","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S0301-0082(99)00016-7","article-title":"Octopamine in invertebrates","volume":"59","author":"T. 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