ArticlePLoS genetics2020
A fly model establishes distinct mechanisms for synthetic CRISPR/Cas9 sex distorters.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 64 citations in OpenAlex.
- Sex distorter male drive for resistance-resilient population control of the human malaria vector Anopheles gambiae.Nature communications · 2026Article
- Genetic engineering for SIT application: a fruit fly-focused review.Insect science · 2026Review
- A male-drive female-sterile system for the self-limited control of the malaria mosquito Anopheles gambiae.Nature communications · 2025Article
- A Comparative Assessment of Self-limiting Genetic Control Strategies for Population Suppression.Molecular biology and evolution · 2025Article
- Advancements and Future Prospects of CRISPR-Cas-Based Population Replacement Strategies in Insect Pest Management.Insects · 2024Review
- Investigating the potential of X chromosome shredding for mouse genetic biocontrol.Scientific reports · 2024Article
- Targeting mosquito X-chromosomes reveals complex transmission dynamics of sex ratio distorting gene drives.Nature communications · 2024Article
- Y chromosome shredding in Anopheles gambiae: Insight into the cellular dynamics of a novel synthetic sex ratio distorter.PLoS genetics · 2024Article
- Germline Cas9 promoters with improved performance for homing gene drive.Nature communications · 2024Article
- The haplolethal gene wupA of Drosophila exhibits potential as a target for an X-poisoning gene drive.G3 (Bethesda, Md.) · 2024Article
- Gene drive and genetic sex conversion in the global agricultural pest Ceratitis capitata.Nature communications · 2024Article
- Gene drive designs for efficient and localisable population suppression using Y-linked editors.PLoS genetics · 2022Article
- A CRISPR endonuclease gene drive reveals distinct mechanisms of inheritance bias.Nature communications · 2022Article
- Selective targeting of biting females to control mosquito-borne infectious diseases.Trends in parasitology · 2022Review
- Natural and Engineered Sex Ratio Distortion in Insects.Frontiers in ecology and evolution · 2022Article
- Gene drives gaining speed.Nature reviews. Genetics · 2022Review
- Manipulating Insect Sex Determination Pathways for Genetic Pest Management: Opportunities and Challenges.Frontiers in bioengineering and biotechnology · 2022Review
- Exploiting a Y chromosome-linked Cas9 for sex selection and gene drive.Nature communications · 2021Article
- Gene drive that results in addiction to a temperature-sensitive version of an essential gene triggers population collapse inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- CRISPR-Cas9 effectors facilitate generation of single-sex litters and sex-specific phenotypes.Nature communications · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Synthetic sex distorters have recently been developed in the malaria mosquito, relying on endonucleases that target the X-chromosome during spermatogenesis. Although inspired by naturally-occurring traits, it has remained unclear how they function and, given their potential for genetic control, how portable this strategy is across species. We established Drosophila models for two distinct mechanisms for CRISPR/Cas9 sex-ratio distortion-"X-shredding" and "X-poisoning"-and dissected their target-site requirements and repair dynamics. X-shredding resulted in sex distortion when Cas9 endonuclease activity occurred during the meiotic stages of spermatogenesis but not when Cas9 was expressed from the stem cell stages onwards. Our results suggest that X-shredding is counteracted by the NHEJ DNA repair pathway and can operate on a single repeat cluster of non-essential sequences, although the targeting of a number of such repeats had no effect on the sex ratio. X-poisoning by contrast, i.e. targeting putative haplolethal genes on the X chromosome, induced a high bias towards males (>92%) when we directed Cas9 cleavage to the X-linked ribosomal target gene RpS6. In the case of X-poisoning sex distortion was coupled to a loss in reproductive output, although a dominant-negative effect appeared to drive the mechanism of female lethality. These model systems will guide the study and the application of sex distorters to medically or agriculturally important insect target species.
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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.