Evidence map›Paper›PMID 42115602›Full record

ArticleNature communications2026

Integrating multiplexing into confineable gene drives effectively overrides resistance in Anopheles stephensi.

Mireia Larrosa-Godall, Lewis Shackleford, Matthew P Edgington, Philip T Leftwich, James C Y Luk, Joshua Southworth, Stewart Rosell, Jake T Creasey, Jack M Aked, Katherine Nevard and 7 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Mireia Larrosa-GodallDepartment of Biology, University of York, Wentworth Way, York, UK.
Lewis ShacklefordDepartment of Biology, University of York, Wentworth Way, York, UK.
Matthew P EdgingtonDepartment of Biology, University of York, Wentworth Way, York, UK.
Philip T LeftwichSchool of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, UK.ORCID http://orcid.org/0000-0001-9500-6592
James C Y LukDepartment of Biology, University of York, Wentworth Way, York, UK.
Joshua SouthworthArthropod Genetics, The Pirbright Institute, Pirbright, UK.
Stewart RosellArthropod Genetics, The Pirbright Institute, Pirbright, UK.ORCID http://orcid.org/0009-0003-2609-9248
Jake T CreaseyDepartment of Biology, University of York, Wentworth Way, York, UK.ORCID http://orcid.org/0000-0002-1450-298X
Jack M AkedDepartment of Biology, University of York, Wentworth Way, York, UK.
Katherine NevardArthropod Genetics, The Pirbright Institute, Pirbright, UK.ORCID http://orcid.org/0000-0002-1008-6587
Alexander DoddsDepartment of Biology, University of York, Wentworth Way, York, UK.
Morgan MckeeDepartment of Biology, University of York, Wentworth Way, York, UK.
Eunice AdedejiDepartment of Biology, University of York, Wentworth Way, York, UK.
Estela GonzalezArthropod Genetics, The Pirbright Institute, Pirbright, UK.ORCID http://orcid.org/0000-0002-4296-0080
Joshua X D AngDepartment of Biology, University of York, Wentworth Way, York, UK.ORCID http://orcid.org/0000-0002-4710-8831
Michelle A E AndersonDepartment of Biology, University of York, Wentworth Way, York, UK. michelle.anderson@york.ac.uk.ORCID http://orcid.org/0000-0003-1510-2942
Luke AlpheyDepartment of Biology, University of York, Wentworth Way, York, UK. luke.alphey@york.ac.uk.ORCID http://orcid.org/0000-0002-2916-3802

Funding

Bill & Melinda Gates Foundation INV-008549Gates Foundation INV-008549RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BBS/E/I/00007033, BBS/E/I/00007038, BBS/E/I/00007039
6 · The paper itself

Abstract

Anopheles stephensi is a major malaria vector mainly present in southern Asia and the Arabian Peninsula. Since 2012 it has invaded several countries of eastern Africa, stimulating urgent efforts to develop more efficient strategies for vector control such as CRISPR/Cas9-based homing gene drives. Target site resistance due to end-joining repair is a significant challenge to the deployment of these systems. The use of multiple sgRNAs has the potential to solve this issue. Here we perform experimental crosses to assess the homing and cutting efficiency of both classical (e.g. four adjacent sgRNAs all in one construct) and additive (e.g. separate constructs each expressing a single sgRNA) multiplexing strategies targeting the cardinal locus, in the presence and absence of a resistance allele. We find resistance alleles at one sgRNA target site can be mitigated by the presence of the additional sgRNAs with either strategy, and do not significantly reduce the homing efficiency for either strategy, validating their effectiveness. Further modelling using parameters derived from the strains generated indicates that while both strategies can overcome resistance allele formation, the fitness of the drive-carrying alleles is a critical factor in determining the overall performance and persistence of a split drive.

Indexed as

AnophelesGene Drive TechnologyInsecticide ResistanceMosquito ControlMosquito VectorsAllelesAnimalsCRISPR-Cas SystemsMalariaRNA, Guide, CRISPR-Cas SystemsRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID42115602
PMCPMC13388953

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.