ArticlePLoS genetics2021
Resistance to a CRISPR-based gene drive at an evolutionarily conserved site is revealed by mimicking genotype fixation.
Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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.
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.
Who cites it
30 citing papers in PubMed.
- The nanosd integral gene drive enables population modification of the malaria vector Anopheles gambiae.G3 (Bethesda, Md.) · 2026Article
- Engineering resilient gene drives for sustainable malaria control by predicting, testing and overcoming target site resistance in Anopheles gambiae.PLoS biology · 2026Article
- Advancements in CRISPR-Cas Systems for Genome Editing towards Eradication of Human Microbial Pathogens.Molecular biotechnology · 2026Review
- Assessing target genes for homing suppression gene drive.The EMBO journal · 2026Article
- Leveraging DNA repair mechanisms in genetically engineered biocontrol.Current opinion in insect science · 2026Review
- Article
- Engineering gene drive docking sites in a haplolethal locus in Anopheles gambiae.Scientific reports · 2025Article
- The Spatial Spread and the Persistence of Gene Drives Are Affected by Demographic Feedbacks, Density Dependence and Allee Effects.Molecular ecology · 2025Article
- CRISPR technologies for the control and study of malaria-transmitting anopheline mosquitoes.Parasites & vectors · 2025Review
- A Comparative Assessment of Self-limiting Genetic Control Strategies for Population Suppression.Molecular biology and evolution · 2025Article
- Engineering drive-selection balance for localized population suppression with neutral dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Challenges in developing a split drive targeting dsx for the genetic control of the invasive malaria vector Anopheles stephensi.Parasites & vectors · 2025Article
- Evaluating the cost of malaria elimination by Anopheles gambiae precision guided SIT in the Upper River region, The Gambia.PLOS global public health · 2025Article
- Cas12f1 gene drives propagate efficiently in herpesviruses and induce minimal resistance.Genome biology · 2024Article
- Genomic analyses revealed low genetic variation in the intron-exon boundary of the doublesex gene within the natural populations of An. gambiae s.l. in Burkina Faso.BMC genomics · 2024Article
- CRISPR-Cas9 and Cas12a target site richness reflects genomic diversity in natural populations of Anopheles gambiae and Aedes aegypti mosquitoes.BMC genomics · 2024Article
- Eliminating malaria vectors with precision-guided sterile males.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Considerations for first field trials of low-threshold gene drive for malaria vector control.Malaria journal · 2024Review
- Modelling daisy quorum drive: A short-term bridge across engineered fitness valleys.PLoS genetics · 2024Article
- Investigating the mechanisms underlying resistance to chemoterapy and to CRISPR-Cas9 in cancer cell lines.Scientific reports · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
CRISPR-based homing gene drives can be designed to disrupt essential genes whilst biasing their own inheritance, leading to suppression of mosquito populations in the laboratory. This class of gene drives relies on CRISPR-Cas9 cleavage of a target sequence and copying ('homing') therein of the gene drive element from the homologous chromosome. However, target site mutations that are resistant to cleavage yet maintain the function of the essential gene are expected to be strongly selected for. Targeting functionally constrained regions where mutations are not easily tolerated should lower the probability of resistance. Evolutionary conservation at the sequence level is often a reliable indicator of functional constraint, though the actual level of underlying constraint between one conserved sequence and another can vary widely. Here we generated a novel adult lethal gene drive (ALGD) in the malaria vector Anopheles gambiae, targeting an ultra-conserved target site in a haplosufficient essential gene (AGAP029113) required during mosquito development, which fulfils many of the criteria for the target of a population suppression gene drive. We then designed a selection regime to experimentally assess the likelihood of generation and subsequent selection of gene drive resistant mutations at its target site. We simulated, in a caged population, a scenario where the gene drive was approaching fixation, where selection for resistance is expected to be strongest. Continuous sampling of the target locus revealed that a single, restorative, in-frame nucleotide substitution was selected. Our findings show that ultra-conservation alone need not be predictive of a site that is refractory to target site resistance. Our strategy to evaluate resistance in vivo could help to validate candidate gene drive targets for their resilience to resistance and help to improve predictions of the invasion dynamics of gene drives in field populations.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.