Engineering drive-selection balance for localised population suppression with neutral dynamics DOI Creative Commons
Katie Willis, Austin Burt

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 21, 2024

Abstract Whilst the release of sterile males has been highly successful in suppressing some pest populations, it is impractical for other 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 localised. One way achieve would have perfect balance, all construct frequencies, between drive increasing and selection decreasing it. Here we describe create balance involving toxin-antidote causes recessive lethality, encodes genomic editor makes dominant lethal edits genome, provides protection against action or consequences editing. Computer modelling shows design 100-fold than males, 1000-fold when released alongside booster. We designs CRISPR-based molecular construction, including options avoid using recoded genes as antidotes.

Язык: Английский

SYNCAS: Efficient CRISPR/Cas9 gene-editing in difficult to transform arthropods DOI Creative Commons
Sander De Rouck, Antonio Mocchetti, Wannes Dermauw

и другие.

Insect Biochemistry and Molecular Biology, Год журнала: 2024, Номер 165, С. 104068 - 104068

Опубликована: Янв. 1, 2024

The genome editing technique CRISPR/Cas9 has led to major advancements in many research fields and this state-of-the-art tool proven its use genetic studies for various arthropods. However, most transformation protocols rely on microinjection of component into embryos, a method which is challenging species. Alternatively, injections can be performed adult females, but efficiencies very low as was shown the two-spotted spider mite, Tetranychus urticae, minute important chelicerate pest crops. In study, we explored different formulations optimize maternal injection protocol T. urticae. We observed strong synergy between branched amphipathic peptide capsules saponins, resulting significant increase knock-out efficiency, exceeding 20%. This formulation, termed SYNCAS, used urticae genes – phytoene desaturase, CYP384A1 Antennapedia also allowed develop co-CRISPR strategy facilitated generation knock-in mutants. addition, SYNCAS successfully applied white white-like western flower thrips, Frankliniella occidentalis. allows routine these species game changer other hard transform

Язык: Английский

Процитировано

19
A Y chromosome-linked genome editor for efficient population suppression in the malaria vector Anopheles gambiae DOI Creative Commons
Ignacio Tolosana, Katie Willis, Matthew O. Gribble

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 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.

Язык: Английский

Процитировано

2
Gene drive and genetic sex conversion in the global agricultural pest Ceratitis capitata DOI Creative Commons
Angela Meccariello, Shibo Hou, Serafima Davydova

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 8, 2024

Homing-based gene drives are recently proposed interventions promising the area-wide, species-specific genetic control of harmful insect populations. Here we characterise a first set in tephritid agricultural pest species, Mediterranean fruit fly Ceratitis capitata (medfly). Our results show that medfly is highly amenable to homing-based drive strategies. By targeting transformer gene, also demonstrate how CRISPR-Cas9 can be coupled sex conversion, whereby females transformed into fertile and harmless XX males. Given this unique malleability determination, modelled couple conversion female sterility found such approaches could effective tolerant resistant allele selection target population. open door for developing strains population suppression related pests by co-targeting reproduction shifting reproductive ratio towards They untapped potential tackle an environmentally friendly economical way.

Язык: Английский

Процитировано

13
Germline Cas9 promoters with improved performance for homing gene drive DOI Creative Commons
Jie Du, W.-C. Chen,

Xihua Jia

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 29, 2024

Abstract Gene drive systems could be a viable strategy to prevent pathogen transmission or suppress vector populations by propagating alleles with super-Mendelian inheritance. CRISPR-based homing gene drives convert wild type into in heterozygotes Cas9 and gRNA. It is thus desirable identify promoters that yield high conversion rates, minimize the formation rate of resistance both germline early embryo, limit somatic expression. In Drosophila , nanos promoter avoids leaky expression, but at cost embryo from maternally deposited Cas9. To improve efficiency, we test eleven melanogaster promoters. Some achieve higher efficiency minimal resistance, none completely avoid However, such expression often does not carry detectable fitness costs for rescue targeting haplolethal gene, suggesting conversion. Supporting 4-gRNA suppression drive, one leads low equilibrium frequency due other outperforms resulting successful cage population. Overall, these hold advantages species may possess valuable homologs organisms.

Язык: Английский

Процитировано

10
CRISPR/Cas9-mediated knockout of Tektin 4-like gene (TEKT4L) causes male sterility of Cydia pomonella DOI
Zihan Wei, Chang Wang, Xinyue Zhang

и другие.

Insect Biochemistry and Molecular Biology, Год журнала: 2025, Номер 177, С. 104257 - 104257

Опубликована: Янв. 5, 2025

Язык: Английский

Процитировано

1
Gene drive-based population suppression in the malaria vector Anopheles stephensi DOI Creative Commons
Xuejiao Xu,

Jingheng Chen,

You Wang

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 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.

Язык: Английский

Процитировано

1
Challenges in developing a split drive targeting dsx for the genetic control of the invasive malaria vector Anopheles stephensi DOI Creative Commons
Mireia Larrosa‐Godall, Joshua X. D. Ang, Philip T. Leftwich

и другие.

Parasites & Vectors, Год журнала: 2025, Номер 18(1)

Опубликована: Фев. 7, 2025

Abstract Background Anopheles stephensi is a competent malaria vector mainly present in southern Asia and the Arabian Peninsula. Since 2012, it has invaded several countries of eastern Africa, creating an emerging risk urban transmission. Urgent efforts are required to develop novel more efficient strategies for targeted control. CRISPR/Cas9-based homing gene drives have been proposed as attractive alternative strategies. Gene potential spread desired trait through population at higher rates than via normal Mendelian inheritance, even presence fitness cost. Several target genes suggested tested different mosquito species such gambiae Aedes aegypti . promising suppression developed An. that sex determination doublesex ( dsx ). Methods In this study, geographically confineable drive system targeting was gRNA Here, transgenic line which expresses Cas9 under control endogenous zpg promoter generated. Separately female specific exon inserted into same site. The reproductive males females heterozygous homozygous element determined. A series experimental crosses performed combine two elements assess rate split system. Results able home super-Mendelian comparable those obtained by autonomous species. Although inheritance high 99.8% were observed, potentially providing very potent drive, dominant effects on male fertility would be sufficient hinder drive. Molecular analysis indicated expressing insertion disrupted splicing Conclusions These results should considered when proposing viability defects found both carrying transgene likely prohibit from functioning field. Graphical

Язык: Английский

Процитировано

1
Genome editing in pests: basic science to applications DOI
Xien Chen, Subba Reddy Palli

Journal of Pest Science, Год журнала: 2024, Номер 97(3), С. 1135 - 1152

Опубликована: Янв. 24, 2024

Язык: Английский

Процитировано

7
Population suppression by release of insects carrying a dominant sterile homing gene drive targeting doublesex in Drosophila DOI Creative Commons
W.-C. Chen,

Jialiang Guo,

Yiran Liu

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Сен. 14, 2024

Язык: Английский

Процитировано

7
A self-limiting sterile insect technique alternative for Ceratitis capitata DOI Creative Commons
Serafima Davydova, Junru Liu, Yiran Liu

и другие.

BMC Biology, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 12, 2025

Genetic biocontrol systems have broad applications in population control of insects implicated both disease spread and food security. Ceratitis capitata (the Mediterranean fruit fly), a major agricultural pest with global distribution, is one the appealing targets for such genetic control. In this study, we establish characterise novel split-CRISPR/Cas9 system term Sex Conversion Induced by CRISPR (SCIC) C. capitata. Using white eye gene toolkit selection achieved up to 100% CRISPR/Cas9 efficiency, displaying feasibility using constitutive promoters. We then induce sex conversion targeting transformer SCIC approach aimed SIT-mediated releases upon radiation-based sterilisation. Knock-out induced partial full female-to-male conversion, remaining individuals all being intersex sterile. modelling shows strong potential outcompete traditional SIT, allowing faster elimination fewer released sterile males. Overall, construct an appropriate use C Our results build foundation further methods species related tephritid pests.

Язык: Английский

Процитировано

0