Full title: Synthetic Homing Endonuclease Gene Drives to Revolutionise Aedes aegypti Biocontrol - Game Changer or Pipe Dream?

Current Opinion in Insect Science, Год журнала: 2025, Номер unknown, С. 101373 - 101373

Опубликована: Апрель 1, 2025

Язык: Английский

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Applications and status of gene drive in plants

PLoS Biology, Год журнала: 2025, Номер 23(4), С. e3003148 - e3003148

Опубликована: Апрель 15, 2025

Gene drive can modify or suppress plant populations, offering solutions to challenges associated with globalization and climate change. However, common features of biology complicate its application. Self-limiting methods provide a controlled, reversible path forward.

Язык: Английский

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Risk management recommendations for environmental releases of gene drive modified insects

Biotechnology Advances, Год журнала: 2021, Номер 54, С. 107807 - 107807

Опубликована: Июль 25, 2021

The ability to engineer gene drives (genetic elements that bias their own inheritance) has sparked enthusiasm and concerns. Engineered could potentially be used address long-standing challenges in the control of insect disease vectors, agricultural pests invasive species, or help rescue endangered species. However, risk concerns uncertainty associated with potential environmental release drive modified insects (GDMIs) have led some stakeholders call for a global moratorium on such releases application other strict precautionary measures mitigate perceived assessment management challenges. Instead, we provide recommendations may improve relevance frameworks GDMIs. These include: (1) developing additional more practical guidance ensure appropriate levels safety; (2) making policy goals regulatory decision-making criteria operational use so what constitutes harm is clearly defined; (3) ensuring dynamic interplay between manage through closely interlinked pre-release modelling post-release monitoring; (4) considering risks against benefits, comparing them those alternative actions account wider (management) context; (5) implementing modular, phased approach authorisations incremental acceptance uncertainty. Along providing stakeholder engagement opportunities analysis process, proposed enable managers make choices are proportionate adaptive risks, benefits GDMI applications, socially robust.

Язык: Английский

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Harnessing Wolbachia cytoplasmic incompatibility alleles for confined gene drive: A modeling study

PLoS Genetics, Год журнала: 2023, Номер 19(1), С. e1010591 - e1010591

Опубликована: Янв. 23, 2023

Wolbachia are maternally-inherited bacteria, which can spread rapidly in populations by manipulating reproduction. cifA and cifB genes found phage that responsible for cytoplasmic incompatibility, the most common type of reproductive interference. In this phenomenon, no viable offspring produced when a male with both (or just some systems) mates female lacking cifA. Utilizing feature, we propose new types toxin-antidote gene drives be constructed only these two an insect genome, instead whole bacteria. By using mathematical simulation models, drive containing together creates confined moderate to high introduction threshold. When introduced separately, they act as self-limiting drive. We observed performance is substantially influenced various ecological parameters characteristics. Extending our models continuous space, individual release distribution has critical impact on persistence. Our results suggest based transgenes safe flexible candidates genetic modification populations.

Язык: Английский

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Acetylcholine esterase of Drosophila melanogaster: a laboratory model to explore insecticide susceptibility gene drives

Pest Management Science, Год журнала: 2024, Номер 80(6), С. 2950 - 2964

Опубликована: Фев. 12, 2024

Abstract BACKGROUND One of the proposed applications gene drives has been to revert pesticide resistant mutations back ancestral susceptible state. Insecticides that have become ineffective because rise resistance could reinvigorated utility and be used suppress pest populations again, perhaps at lower application doses. RESULTS We created a laboratory model for susceptibility replaces field‐selected variants acetylcholine esterase ( Ace ) locus Drosophila melanogaster with variants. constructed CRISPR/Cas9 homing drive found occurred in many genetic backgrounds varying efficiencies. While itself not homozygous, it converted alleles into ones produced recessive lethal populations. Our studies provided evidence two distinct classes (GDR): rather than being mediated by conventional non‐homologous end‐joining (NHEJ) pathway, one seemed involve short homologous repair other was defined background. Additionally, we simulations explore drives; use chemicals prevent spread synthetic protected areas. CONCLUSIONS Insecticide useful tools control insects however problems particularities target loci GDR will need overcome them effective. Furthermore, realistic patterns dispersal high insecticide exposure rates would required if were as ‘safety‐switch’ unwanted drives. © 2024 The Authors. Pest Management Science published John Wiley & Sons Ltd on behalf Society Chemical Industry.

Язык: Английский

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A genome-wide CRISPR screen in Anopheles mosquito cells identifies essential genes and required components of clodronate liposome function

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

Опубликована: Сен. 24, 2024

mosquitoes are the sole vector of human malaria, most burdensome vector-borne disease worldwide. Strategies aimed at reducing mosquito populations and limiting their ability to transmit show promise for control. Therefore, gaining an improved understanding biology, specifically that immune response, can aid efforts develop new approaches limit malaria transmission. Here, we use a genome-wide CRISPR screening approach first time in cells identify essential genes

Язык: Английский

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Testing non-autonomous antimalarial gene drive effectors using self-eliminating drivers in the African mosquito vector Anopheles gambiae

PLoS Genetics, Год журнала: 2022, Номер 18(6), С. e1010244 - e1010244

Опубликована: Июнь 2, 2022

Gene drives for mosquito population modification are novel tools malaria control. Strategies to safely test antimalarial effectors in the field required. Here, we modified Anopheles gambiae zpg locus host a CRISPR/Cas9 integral gene drive allele ( D ) and characterized its behaviour resistance profile. We found that dominantly sterilizes females but can induce efficient at other loci when it itself encounters resistance. combined with multiple previously non-autonomous payload that, as self-eliminates, leads conversion of cage populations these loci. Our results demonstrate how self-eliminating drivers could allow safe testing effector-traits by local modification. They also suggest after engendering resistance, intended suppression nevertheless serve propagate subsequently released genes, allowing vector initially targeted suppression.

Язык: Английский

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Engineering drive-selection balance for localised population suppression with neutral dynamics

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

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Altering traits and fates of wild populations with Mendelian DNA sequence modifying Allele Sails

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

Опубликована: Авг. 13, 2024

Population-scale genome modification can alter the composition or fate of wild populations. Synthetic gene drives provide one set tools, but their use is complicated by scientific, regulatory, and social issues associated with transgene persistence flow. Here we propose an alternative approach. An Allele Sail consists a editor (the Wind) that introduces DNA sequence edits, inherited in Mendelian fashion. Meanwhile, edits Sail) experience arithmetic, Super-Mendelian increase frequency. We model this system identify contexts which single, low frequency release brings to very high also conditions manipulation sex determination bring about population suppression. In regulatory frameworks distinguish between transgenics (GMO) edited non-transgenic progeny (non-GMO) Sails may prove useful since spread GM component be limited. authors introduce as method for spreading genetic changes throughout population.

Язык: Английский

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Driving down malaria transmission with engineered gene drives

Frontiers in Genetics, Год журнала: 2022, Номер 13

Опубликована: Окт. 19, 2022

The last century has witnessed the introduction, establishment and expansion of mosquito-borne diseases into diverse new geographic ranges. Malaria is transmitted by female Anopheles mosquitoes. Despite making great strides over past few decades in reducing burden malaria, transmission now on rise again, part owing to emergence mosquito resistance insecticides, antimalarial drug and, more recently, challenges COVID-19 pandemic, which resulted reduced implementation efficiency various control programs. utility genetically engineered gene drive mosquitoes as tools decrease malaria controlling disease-transmitting being evaluated. To date, there been remarkable progress development CRISPR/Cas9-based homing endonuclease designs due successful proof-of-principle multigenerational experiments. In this review, we examine lessons learnt from current drives, providing a framework for systems targeted wild malaria-transmitting populations that overcome such with evolving drive-resistance. We also discuss additional substantial works required scientific discovery further study subsequent field application endemic settings.

Язык: Английский

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