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ToolsHarvey-Samuel, Tim, Kaur, Rajdeep, Leftwich, Philip T., Feng, Xuechun, Gantz, Valentino and Alphey, Luke (2026) Sequence mismatch between gene-drive and target-site flanking regions significantly impairs homing efficiency in Culex quinquefasciatus. Genetics. ISSN 1943-2631
Full text not available from this repository. (Request a copy)Abstract
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 (‘homed’). Homing is dependent on sequence homology between the genomic regions flanking the transgene insertion and the break site. Homing efficiency (i.e. 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 ‘split’ 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 optimisation 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.
| Item Type: | Article |
|---|---|
| Additional Information: | Data Availability: The authors affirm that all data necessary for confirming the conclusions of the article are present within the article, additional information files, figures, and tables. Specifically, all data gathered during and analyzed as part of the two experiments (i.e. inheritance rates of different genotypes, estimation of cutting rates, list of sequenced allele-identities) is available in the two additional information files. Strains and plasmids are available upon request. |
| Uncontrolled Keywords: | homology directed repair,gene-drive,homing endonuclease gene,west nile virus,avian malaria |
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Science > Research Groups > Biosciences Teaching and Education Research |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 09 Apr 2026 16:30 |
| Last Modified: | 09 Apr 2026 16:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/102741 |
| DOI: | 10.1093/genetics/iyag054 |
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