A Y chromosome-linked genome editor for efficient population suppression in the malaria vector Anopheles gambiae

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Abstract Genetic control – the deliberate introduction of genetic traits to a pest or vector population offers powerful tool augment conventional mosquito tools that have been successful in reducing malaria burden but are compromised by range operational challenges. Self-sustaining strategies shown great potential laboratory settings, hesitancy due their invasive and persistent nature may delay implementation. Here, instead, we describe self-limiting strategy, designed geographically temporally restricted effect, based on Y chromosome-linked genome editor (YLE). The YLE comprises CRISPR-Cas9 construct is always inherited males yet generates an autosomal dominant mutation transmitted over 90% offspring results female-specific sterility. To our knowledge, system represents pioneering approach engineering chromosome generate strain for mosquitoes. Mathematical modelling shows this technology up seven times more efficient suppression than optimal versions other strategies, such as widely used Sterile Insect Technique Release Insects carrying Dominant Lethal gene.

Language: Английский

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Assessment of drive efficiency and resistance allele formation of a homing gene drive in the mosquito Aedes aegypti

Journal of Pest Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Language: Английский

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Gene drive-based population suppression in the malaria vector Anopheles stephensi

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 24, 2025

Gene drives are alleles that can bias the inheritance of specific traits in target populations for purpose modification or suppression. Here, we construct a homing suppression drive major urban malaria vector Anopheles stephensi targeting female-specific exon doublesex, incorporating two gRNAs and nanos-Cas9 to reduce functional resistance improve female heterozygote fitness. Our results show was recessive sterile both females males, with various intersex phenotypes homozygotes. Both male heterozygotes only moderate conversion, indicating nanos promoter has lower activity A. than gambiae. By amplicon sequencing, detect very low level allele formation. Combination vasa-Cas9 line boosts conversion rate 100%, suggesting use similar systems population continuous release strategy SIT fsRIDL techniques. This study contributes valuable insights development more efficient environmentally friendly pest control tools aimed at disrupting disease transmission. their spread through populations. constructed efficiency 2-gRNA mosquito doublesex. With vasa-Cas9, high self-limiting achieved.

Language: Английский

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A comprehensive review of biological and genetic control approaches for leishmaniasis vector sand flies; emphasis towards promoting tools for integrated vector management

PLoS neglected tropical diseases, Journal Year: 2025, Volume and Issue: 19(1), P. e0012795 - e0012795

Published: Jan. 27, 2025

Background Leishmaniasis is a health problem in many regions with poor and life resources. According to the World Health Organization (WHO), an estimated 700,000–1 million new cases arise annually. Effective control of sand fly vector populations crucial for reducing transmission this disease. Therefore, review aims comprehensively examine evaluate current methods controlling populations, focusing on biological gene drive techniques. Methods findings A detailed, comprehensive literature search was carried out using databases including Google Scholar, PubMed, ScienceDirect, National Library Medicine (NIH). These searches were done specific keywords related field study. This identified several promising methods, genetically modified flies, transgenic approaches by taking advanced editing tools like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9) genetic modification symbiotic microorganisms which appeared be proven under laboratory settings. Conclusion Genetic have benefits over chemical control, long-lasting effects targets, high specificity, less environmental impact. Advances engineering technologies, particularly CRISPR/Cas9, sterile insect techniques, modification, offer avenues precise efficient management. Future research should prioritize optimizing rearing sterilization conducting controlled trials, fostering collaboration across disciplines realize potential strategies combating leishmaniasis.

Language: Английский

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Engineering drive–selection balance for localized population suppression with neutral dynamics

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(6)

Published: Feb. 4, 2025

While the release of sterile males has been highly successful in suppressing some pest populations, it is impractical for many species due to disappearing after a single generation, necessitating large, repeated releases maintain sufficient impact. Synthetic gene drives promise more efficient approaches since they can increase frequency from rare, yet this also allows them spread across landscape, which may not always be desired. Between these two extremes are selectively neutral genetic constructs persist at released, offering potential suppression that remains localized. One way achieve would have perfect balance, all construct frequencies, between drive increasing and selection decreasing it. Here, we describe closely approximate balance using toxin–antidote causes recessive lethality or sterility, encodes genomic editor makes dominant lethal edits genome, provides protection against action consequences editing. Computer modeling shows design 100-fold than males, 1,000-fold when released alongside booster. We designs CRISPR-based molecular construction, including options avoid recoded genes as antidotes.

Language: Английский

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Nrf2 Signaling Pathway Studies in Drosophila melanogaster : Parallel Roles in Human Health and Insect Environmental Responses

Xenobiotica, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 30

Published: Feb. 11, 2025

The Nrf2 signaling pathway is crucial for cellular defense against oxidative stress and xenobiotic toxicity, highlighting its importance in both human health environmental responses.

Language: Английский

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Stronger population suppression by gene drive targetingdoublesexfrom dominant female-sterile resistance alleles

Published: April 20, 2025

Abstract CRISPR homing drives can be used to suppress a population by targeting female fertility genes. They convert wild-type alleles drive in the germline of heterozygotes homology-directed repair after DNA cleavage. However, resistance produced end-joining pose great threat drive. prevent further recognition Cas9, and therefore weaken suppressive power, or even stop suppression if they preserve function target gene. We multiplexed gRNAs doublesex Drosophila avoid functional create that were dominant female-sterile. This occurred because male dsx transcript was generated females disruption female-specific splicing acceptor site. rescued sterility providing an alternate As desired, recessive sterile yielded high inheritance among progeny both heterozygotes. The dominant-sterile enabled stronger computational models, face modest efficiency fitness costs. we found homozygotes also rescue splice Attempts males with expression arrangements not successful, though some had less severe intersex phenotypes. Though this negatively impacted drive, models showed it still significantly improved power. Therefore, design may have wide applicability -based gene variety organisms intermediate performance.

Language: Английский

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A homing rescue gene drive with multiplexed gRNAs reaches high frequency in cage populations but generates functional resistance

Journal of genetics and genomics/Journal of Genetics and Genomics, Journal Year: 2024, Volume and Issue: 51(8), P. 836 - 843

Published: April 8, 2024

Language: Английский

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