Symbionts and gene drive: two strategies to combat vector-borne disease

Trends in Genetics, Год журнала: 2022, Номер 38(7), С. 708 - 723

Опубликована: Март 21, 2022

Safe and sustainable approaches for mosquito control are critical due to the global increasing burden of mosquito-transmitted diseases.Novel based on symbionts currently proposed modify or suppress populations Wolbachia-based methods have already achieved some success in field trials.Transgenic mosquitoes carrying gene drives that spread through a promising approach block disease transmission vector species.Transgenic-based potentially offer more power flexibility, but symbiont-based usually socially accepted well-developed. Mosquitoes bring health problems by transmitting parasites viruses such as malaria dengue. Unfortunately, current insecticide-based strategies only moderately effective because high cost resistance. Thus, scalable, sustainable, cost-effective needed mosquito-borne control. Symbiont-based genome engineering-based provide new tools show promise meeting these criteria, enabling modification suppression approaches. Symbiotic bacteria like Wolbachia maternally inherited manipulate host reproduction enhance their vertical transmission. Genome drive methods, which genetically altered alleles throughout wild populations, also proving be powerful laboratory. Here, we review latest developments both drive-based methods. We describe notable similarities, well distinctions obstacles, relating technologies. can found almost anywhere world, tropics subtropics, half world's population is under threat pathogens dengue virus (DENV), Zika (ZIKV), chikungunya (CHIKV), yellow fever, West Nile (WNV), malaria, filarial nematodes [1.World Health Organization Working Overcome Global Impact Neglected Tropical Diseases: First WHO Report Diseases. WHO, 2010Google Scholar,2.Tahir D. et al.Vector-borne nematode diseases pets humans Mediterranean Basin: an update.Vet. World. 2019; 12: 1630-1643Crossref PubMed Scopus (15) Google Scholar]. 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(B) fungus-based Wickerhamomyces anomalus secreting toxin protein Beauveria bassiana DENV-2 (ZIKV) activity inducing system. (C) insect-specific (Eilat virus, cell fusing agent Phasi Charoen-like Negevirus) arbovirus development, either alone combination. (D) Engineered AS1 proteins Dirofilaria immitis. (E) Metarhizium pingshaense-infected shorter life spans reproductive output than (F) virus-based Negevirus expressed anti-chikungunya (CHIKV) antibody CHIKV replication.View Large Image Figure ViewerDownload Hi-res image Download (PPT) I). (A) replication. Besides Wolbachia, research made rapid recently 1A,B). field-caught sinensis berghei modulating genes [23.Bai L. al.A gut symbiotic marcescens renders activation immune responses.Front. 1580Crossref interact [24.Cappelli al.Asaia activates eliciting anti-Plasmodium response: control.Front. 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Язык: Английский

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A homing suppression gene drive with multiplexed gRNAs maintains high drive conversion efficiency and avoids functional resistance alleles

G3 Genes Genomes Genetics, Год журнала: 2022, Номер 12(6)

Опубликована: Апрель 8, 2022

Abstract Gene drives are engineered alleles that can bias inheritance in their favor, allowing them to spread throughout a population. They could potentially be used modify or suppress pest populations, such as mosquitoes diseases. CRISPR/Cas9 homing drives, which copy themselves by homology-directed repair drive/wild-type heterozygotes, powerful form of gene drive, but they vulnerable resistance preserve the function target gene. Such prevent successful population suppression. Here, we constructed suppression drive Drosophila melanogaster utilized multiplexed gRNAs inhibit formation functional its female fertility The selected gRNA sites were close together, preventing reduction conversion efficiency. construct reached moderate equilibrium frequency cage populations without apparent alleles. However, fitness cost prevented elimination population, showing importance using highly efficient strategy, even if addressed. Nevertheless, our results experimentally demonstrate viability strategy drives.

Язык: Английский

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Germline Cas9 promoters with improved performance for homing gene drive

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

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Overriding Mendelian inheritance in Arabidopsis with a CRISPR toxin–antidote gene drive that impairs pollen germination

Nature Plants, Год журнала: 2024, Номер 10(6), С. 910 - 922

Опубликована: Июнь 17, 2024

Язык: 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, Год журнала: 2025, Номер unknown

Опубликована: Янв. 8, 2025

Язык: Английский

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Cleave and Rescue gamete killers create conditions for gene drive in plants

Nature Plants, Год журнала: 2024, Номер 10(6), С. 936 - 953

Опубликована: Июнь 17, 2024

Язык: Английский

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Modelling homing suppression gene drive in haplodiploid organisms

Proceedings of the Royal Society B Biological Sciences, Год журнала: 2022, Номер 289(1972)

Опубликована: Апрель 13, 2022

Gene drives have shown great promise for suppression of pest populations. These engineered alleles can function by a variety mechanisms, but the most common is CRISPR homing drive, which converts wild-type to drive in germline heterozygotes. Some potential target species are haplodiploid, males develop from unfertilized eggs and thus only one copy each chromosome. This prevents conversion, substantial disadvantage compared diploids where conversion take place both sexes. Here, we study gene haplodiploids find that targeting female fertility could still be successful. However, such less powerful than suffer more functional resistance alleles. They substantially vulnerable high allele formation embryo owing maternally deposited Cas9 guide RNA also somatic cleavage activity. Examining spatial models organisms move over continuous landscape, haplodiploid surprisingly perform nearly as well diploids, possibly their ability spread further before inducing strong suppression. Together, these results indicate potentially used effectively suppress

Язык: Английский

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Anopheles homing suppression drive candidates exhibit unexpected performance differences in simulations with spatial structure

eLife, Год журнала: 2022, Номер 11

Опубликована: Окт. 14, 2022

Recent experiments have produced several Anopheles gambiae homing gene drives that disrupt female fertility genes, thereby eventually inducing population collapse. Such may be highly effective tools to combat malaria. One such drive, based on the zpg promoter driving CRISPR/Cas9, was able eliminate a cage of mosquitoes. A second version, purportedly improved upon first by incorporating an X-shredder element (which biases inheritance towards male offspring), similarly successful. Here, we analyze experimental data from each these extract their characteristics and performance parameters compare previous interpretations performance. We assess suppression drive within individual-based simulation framework models mosquito dynamics in continuous space. find combined homing/X-shredder is actually less at context our model. In particular, often fails completely suppress population, instead resulting unstable equilibrium between wild-type alleles. By contrast, otherwise similar nos prove more promising candidates for future development than originally thought.

Язык: Английский

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Assessment of distant-site rescue elements for CRISPR toxin-antidote gene drives

Frontiers in Bioengineering and Biotechnology, Год журнала: 2023, Номер 11

Опубликована: Фев. 13, 2023

Gene drive is a genetic engineering technology that can enable super-mendelian inheritance of specific alleles, allowing them to spread through population. New gene types have increased flexibility, offering options for confined modification or suppression target populations. Among the most promising are CRISPR toxin-antidote drives, which disrupt essential wild-type genes by targeting with Cas9/gRNA. This results in their removal, increasing frequency drive. All these drives rely on having an effective rescue element, consists recoded version gene. element be at same site as gene, maximizing chance efficient rescue, distant site, allows useful such easily disrupting another confinement. Previously, we developed homing haplolethal and haplosufficient These successful had functional elements but suboptimal efficiency. Here, attempted construct distant-site configuration from three loci Drosophila melanogaster . We found additional gRNAs cut rates nearly 100%. However, all failed both genes. Furthermore, one minimally sequence was used template homology-directed repair different chromosomal arm, resulting formation resistance alleles. Together, inform design future CRISPR-based drives.

Язык: Английский

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Manipulating the Destiny of Wild Populations Using CRISPR

Annual Review of Genetics, Год журнала: 2023, Номер 57(1), С. 361 - 390

Опубликована: Сен. 19, 2023

Genetic biocontrol aims to suppress or modify populations of species protect public health, agriculture, and biodiversity. Advancements in genome engineering technologies have fueled a surge research this field, with one gene editing technology, CRISPR, leading the charge. This review focuses on current state CRISPR for genetic pests highlights progress ongoing challenges using these approaches.

Язык: Английский

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