{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:49:39Z","timestamp":1785937779214,"version":"3.56.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000268","name":"UK Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BBS\/E\/I\/00007033"],"award-info":[{"award-number":["BBS\/E\/I\/00007033"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"UK Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BBS\/E\/I\/00007038"],"award-info":[{"award-number":["BBS\/E\/I\/00007038"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"UK Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BBS\/E\/I\/00007039"],"award-info":[{"award-number":["BBS\/E\/I\/00007039"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>CRISPR\/Cas9-based homing gene-drives (homing-drives) hold enormous potential as control tools for mosquito disease-vectors. These genomically encoded technologies spread themselves through target populations by creating double-stranded DNA breaks on homologous chromosomes, into which the homing-drives are copied (\u201chomed\u201d). Homing is dependent on sequence homology between the genomic regions flanking the transgene insertion and the break site. Homing efficiency (ie copying rate) substantially impacts the power of these systems: less efficient homing-drives spread slower, have fewer applications, and are more resistance-prone. Understanding what influences homing-drive efficiency is therefore vital to the successful use of these technologies. Here we report a novel mechanism by which a homing-drive's efficiency can be significantly impaired by natural sequence variation within a population into which it is spreading. Using a kmo-targeting \u201csplit\u201d homing-drive in the West Nile virus mosquito Culex quinquefasciatus, we found that target-site heterology (sequence mismatch between the genomic regions flanking the target cut-site and the homing-drive transgene) of less than 10% reduced homing efficiency by up to 54%. While substantial research effort has been dedicated to increasing homing-drive efficiency through optimization of within-construct components, our results highlight that the real-world efficacy of these systems may in part depend on variation beyond these controllable factors.<\/jats:p>","DOI":"10.1093\/genetics\/iyag054","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T18:35:28Z","timestamp":1772562928000},"source":"Crossref","is-referenced-by-count":4,"title":["Sequence mismatch between gene-drive and target-site flanking regions significantly impairs homing efficiency in\n                    <i>Culex quinquefasciatus<\/i>"],"prefix":"10.1093","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8793-3003","authenticated-orcid":false,"given":"Tim","family":"Harvey-Samuel","sequence":"first","affiliation":[{"name":"School of Life Sciences, Keele University , Keele, Staffordshire ST5 5GB ,","place":["United Kingdom"]},{"name":"Arthropod Genetics, The Pirbright Institute , Woking GU24 0NF ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajdeep","family":"Kaur","sequence":"additional","affiliation":[{"name":"Arthropod Genetics, The Pirbright Institute , Woking GU24 0NF ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9500-6592","authenticated-orcid":false,"given":"Philip T","family":"Leftwich","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of East Anglia, Norwich Research Park , Norwich NR4 7TJ ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuechun","family":"Feng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biology of Crop Pathogens and Insects of Zhejiang Province, College of Agriculture and Biotechnology, Zhejiang University , Hangzhou 310027 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