Suppression gene drive in continuous space can result in unstable persistence of both drive and wild‐type alleles

Molecular Ecology, Год журнала: 2021, Номер 30(4), С. 1086 - 1101

Опубликована: Янв. 8, 2021

Abstract Rapid evolutionary processes can produce drastically different outcomes when studied in panmictic population models vs. spatial models. One such process is gene drive, which describes the spread of “selfish” genetic elements through a population. Engineered drives are being considered for suppression disease vectors or invasive species. While laboratory experiments and modelling populations have shown that rapidly eliminate population, it remains unclear if these results translate to natural environments where individuals inhabit continuous landscape. Using spatially explicit simulations, we show release drive result what term “chasing” dynamics, wild‐type recolonize areas has locally eliminated Despite subsequently reconquering areas, complete often fails occur substantially delayed. This increases likelihood lost resistance evolves. We analyse how chasing dynamics influenced by type its efficiency, fitness costs, ecological factors as maximal growth rate levels dispersal inbreeding. find more common lower efficiency low some mechanisms prone behaviour than others. Our demonstrate determined complex interplay factors, highlighting need realistic predict outcome releases populations.

Язык: Английский

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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]. For example, DENV incidence has grown over 30-fold past 50 years, now reaching about 400 million cases per year [3.Bhatt S. al.The distribution dengue.Nature. 2013; 496: 504-507Crossref (5268) The recent ZIKV outbreak resulted hundreds thousands infections large-scale social economic disruption [4.World Virus Outbreak Response: Interim Report. 2016Google While falling southeast Asia, rising other parts world remain 'unacceptably high' according World [5.Guglielmi G. Malaria worldwide.Nature. (Published online December 4, 2019. https://doi.org/10.1038/d41586-019-03746-3)Crossref Re-emergence expansion many factors, including increased urbanization travel trade, climate change, land use pattern changes, unreliable piped water supply [6.World Vector Control Response 2017-2030. 2017Google Current strategies, long-lasting insecticide-treated bed nets, chemical insecticides, environmental management [7.Schreck C.E. Permethrin dimethyl phthalate tent fabric treatments against Aedes aegypti.J. Am. Mosq. Assoc. 1991; 7: 533-535PubMed Scholar], been unable address genetic behavioral resistance interventions [8.Succo T. al.Autochthonous Nîmes, South France, July September 2015.Euro Surveill. 2016; 21: 21Crossref (0) In addition, unintended effect important nontarget insects, pollinators [9.Ware G.W. Effects pesticides organisms.Residue Rev. 1980; 76: 173-201Crossref (49) new, urgently diseases. response this growing need, number novel technologies expanded years. Many involve release aim achieve (see Glossary) type mosquitoes. Population reduce eliminate populations. Such include sterile insect technique (SIT), incompatible (IIT), transgenic-based technologies, where insects mate with sizes next generation. Gene approaches, increase frequency multiple generations, could after single refractory resistant prevent pathogen symbiont into enable result entire becoming pathogen. review, summarize symbiont-infected transgenic focusing different varieties capabilities. early symbiont-mediated [10.Laven H. Eradication Culex pipiens fatigans cytoplasmic incompatibility.Nature. 1967; 216: 383-384Crossref (275) Scholar] was introduction nonmodified microorganisms competence (Box 1). most extensively studied system natural It may common intracellular endosymbiont arthropods nematodes, 60% all harboring [11.Hilgenboecker K. al.How species infected Wolbachia?--A statistical analysis data.FEMS Microbiol. Lett. 2008; 281: 215-220Crossref transmitted vertically from mother offspring maximize manipulating feminization, parthenogenesis, male killing, and/or incompatibility (CI). CI induced when Wolbachia-infected males uninfected females, results nonviable offspring. inhibit infection DENV, ZIKV, arboviruses, parasite (Figure 1, Key figure ) [12.Bian al.Wolbachia invades Anopheles stephensi induces refractoriness Plasmodium infection.Science. 340: 748-751Crossref (289) Scholar, 13.Dutra H.L. blocks circulating isolates Brazilian aegypti mosquitoes.Cell Host Microbe. 19: 771-774Abstract Full Text PDF 14.Hughes G.L. virulent human falciparum gambiae.PLoS Pathog. 2011; 7e1002043Crossref (214) Transfected native used Scholar,15.Zheng X. al.Incompatible techniques combined mosquitoes.Nature. 572: 56-61Crossref (212) Interestingly, species, aegypti, naturally free [16.Gloria-Soria A. al.Lack evidence (Diptera: Culicidae).J. Med. Entomol. 2018; 55: 1354-1356PubMed Scholar,17.Ross P.A. al.An elusive endosymbiont: does occur aegypti?.Ecol. Evol. 2020; 10: 1581-1591Crossref (27) providing open niche infection. there conjecture if major vectors truly [18.Chrostek E. 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Commun. 4388Crossref 22.Caragata E.P. translational science: controlling pathogens.Trends Parasitol. 37: 1050-1067Abstract Scholar].Box 1Using strategiesThe increasingly emerging interactions among hosts, infection, inspiring development [111.Gupta Nair Dynamics insect-microbiome interaction influence microbial symbiont.Front. 11: 1357Crossref (25) Most importantly, shows potential minimize problem cause minimal side effects application includes: (i) delivering directly disrupt physiology display antipathogen effects; (ii) express effector molecules, then engineered so decreased [112.Gao al.Mosquito microbiota implications control.Trends 36: 98-111Abstract (28) vectorial capacity [113.Cansado-Utrilla C. microbiome capacity: rich discovery translation.Microbiome. 9: 111Crossref (9) I).Figure 1Key figure. control.Show full caption(A) Natural bacteria-based (CI) Serratia Y1 Asaia induce immunity slow development. secondary metabolites ureilytica Su_YN1 Chromobacterium responsible antiplasmodial (DENV)-2. (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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U. 2007; 104: 9047-9051Crossref (296) Recently, successfully conditionally scorpine, significantly parasites, displaying reduced compared stain constitutively expressing [41.Shane J.L. al.Blood meal-induced inhibition microbiota.Nat. 4127Crossref (31) More recently, within heartworm immitis [42.Epis al.Chimeric stimulate development.Commun. 3: 105Crossref Notably, keep capability laboratory semi-field conditions Intriguingly, appear antagonistic one another. showed lower densities counterparts, removing enabled [43.Rosso al.Reduced diversity two areas invasion.Sci. 16091Crossref Scholar,44.Hughes al.Native impedes mosquitoes.Proc. 2014; 111: 12498-12503Crossref (137) Genetically pingshaense (Mp-hybrid) coluzzii had lifespans Mp-hybrid higher virulence inoculum load trial Faso Finally, modifying Negevirus, anti-CHIKV antibodies inhibited bacteria, fungus, even existing basis identified compelling genes, cifA cifB, involved induction rescue. models mechanism(s) still elucidated, expression bacterial germline recapitulate phenotype. Expression females rescues CI, intriguingly, appears coexpression cifB required [45.Beckmann J.F. deubiquitylating enzyme incompatibility.Nat. 2: 17007Crossref (181) Scholar,46.LePage D.P. al.Prophage WO Wolbachia-induced 543: 243-247Crossref (218) phenotypes replicated crosses between cif studies examining molecular accomplished flies 46.LePage 47.Shropshire J.D. al.One prophage Drosophila melanogaster.Proc. 115: 4987-4991Crossref (82) 48.Shropshire al.Evolution-guided mutagenesis proteins: identifying CifA's complex functional repertoire essential regions CifB.PLoS 16e1008794Crossref (11) recapitulated wPip (though here, CI) [49.Adams K.L. vector.Nat. M

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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Gene Drive Dynamics in Natural Populations: The Importance of Density Dependence, Space, and Sex

Annual Review of Ecology Evolution and Systematics, Год журнала: 2020, Номер 51(1), С. 505 - 531

Опубликована: Авг. 28, 2020

The spread of synthetic gene drives is often discussed in the context panmictic populations connected by flow and described with simple deterministic models. Under such assumptions, an entire species could be altered releasing a single individual carrying invasive drive, as standard homing drive. While this remains theoretical possibility, drive natural more complex merits realistic assessment. fate any released population would inextricably linked to ecology population. Given uncertainty involved ecological assessment populations, understanding sensitivity important factors critical. Here we review how different forms density-dependence, spatial heterogeneity mating behaviors can impact self-sustaining drives. We highlight specific aspects dynamics target that need further research.

Язык: Английский

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CRISPR-based genetic control strategies for insect pests

Journal of Integrative Agriculture, Год журнала: 2022, Номер 22(3), С. 651 - 668

Опубликована: Ноя. 16, 2022

Genetic control strategies such as the sterile insect technique have successfully fought pests worldwide. The CRISPR (clustered regularly interspaced short palindromic repeats) technology, together with high-quality genomic resources obtained in more and species, greatly facilitates development of novel genetic strains that can be used area-wide species-specific pest programs. Here, we review research progress towards state-of-art CRISPR-based strategies, including gene drive, sex ratio distortion, CRISPR-engineered sexing strains, precision-guided technique. These strategies' working mechanisms, potential resistance regulations are illustrated discussed. In addition, recent developments stacked conditional systems introduced. We envision advances technology will continue to one driving forces for developing next generation strategies.

Язык: Английский

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Adversarial interspecies relationships facilitate population suppression by gene drive in spatially explicit models

Ecology Letters, Год журнала: 2023, Номер 26(7), С. 1174 - 1185

Опубликована: Май 10, 2023

Suppression gene drives bias their inheritance to spread through a population, potentially eliminating it when they reach high frequency. CRISPR homing suppression have already seen success in the laboratory, but several models predict that may be elusive population with realistic spatial structure due extinction-recolonization cycles. Here, we extend our continuous space framework include two competing species or predator-prey pairs. We find both general and mosquito-specific models, predators can facilitate drive-based suppression, albeit at cost of an increased rate drive loss outcomes. These results are robust mosquito seasonal fluctuations. Our study illustrates difficulty predicting outcomes complex ecosystems. However, promising for prospects less powerful successfully eliminate target other pest populations.

Язык: Английский

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Population suppression by release of insects carrying a dominant sterile homing gene drive targeting doublesex in Drosophila

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

Опубликована: Сен. 14, 2024

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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Adequacy and sufficiency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post‐market environmental monitoring of genetically modified insects containing engineered gene drives

EFSA Journal, Год журнала: 2020, Номер 18(11)

Опубликована: Ноя. 1, 2020

Advances in molecular and synthetic biology are enabling the engineering of gene drives insects for disease vector/pest control.Engineered (that bias their own inheritance) can be designed either to suppress interbreeding target populations or modify them with a new genotype.Depending on engineered drive system, theoretically, genetic modification interest could spread through persist indefinitely, restricted its persistence.While research applications is advancing at fast pace, it will take several years technological developments move practical deliberate release into environment.Some modified (GDMIs) have been tested experimentally laboratory, but none has assessed small-scale confined field trials open as yet.There concern that GDMIs environment may possible irreversible unintended consequences.As proactive measure, European Food Safety Authority (EFSA) requested by Commission review whether previously published guidelines risk assessment genetically animals (EFSA, 2012 2013), including (GMIs), adequate sufficient GDMIs, primarily vectors, agricultural pests invasive species, environment.Under this mandate, EFSA was not develop GDMIs.In Scientific Opinion, Panel Genetically Modified Organisms (GMO) concludes EFSA's adequate, insufficient characterisation (MC), environmental (ERA) post-market monitoring (PMEM) GDMIs.While MC, ERA PMEM build existing framework GMIs do contain drives, there specific areas where further guidance needed GDMIs.

Язык: Английский

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