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

Trends in Genetics, Journal Year: 2022, Volume and Issue: 38(7), P. 708 - 723

Published: March 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. Gerth M. Is gambiae Wolbachia?.mBio. 10e00784-19Crossref (24) reports indicate Anopheline possess high-density [19.Walker al.Stable moucheti demeilloni mosquitoes.Curr. Biol. 2021; 31: 2310-2320Abstract (12) This offers renewed medically relevant strains adapted environment. Several reviews covered progress exploit bacterium [20.Flores H.A. O'Neill S.L. Controlling vector-borne releasing modified mosquitoes.Nat. 16: 508-518Crossref (145) 21.Wang G.-H. al.Combating using technologies.Nat. 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. Genet. 836Crossref (20) Symbionts not interfere pathogens, they directly. secretes antimalarial lipase kills at stages, effectively preventing [25.Gao via secretion lipase.Nat. 6: 806-817Crossref (6) [26.Wu P. commensal promotes permissiveness arboviruses.Cell 25: 101-112Abstract (76) Likewise, inhibits midgut growth displays entomopathogenic larvae adults. Romidepsin might metabolite [27.Saraiva R.G. al.Chromobacterium spp. mediate histone deacetylase inhibitor romidepsin.Sci. Rep. 8: 6176Crossref (23) Scholar]; aminopeptidase interferes attachment degradation Flavivirus E [28.Saraiva al.Aminopeptidase secreted sp. Panama degrading protein.PLoS Negl. Trop. Dis. 12e0006443Crossref fungi yeast killer strong developmental stages [29.Cappelli al.Killer yeasts exert anti-plasmodial activities mice.Parasite Vector. 329Crossref Toll/Jak-Stat pathways reduces [30.Dong Y. fungus activate toll JAK-STAT pathway-controlled anti-dengue aegypti.Insect Biochem. Mol. 2012; 42: 126-132Crossref (80) albopictus [31.Deng S.Q. al.Beauveria virus.J. Pest. Sci. 92: 781-789Crossref (8) Beyond fungi, (ISVs) arboviruses. Cell (CFAV) recognized ISV cells phenotype [32.Stollar V. Thomas V.L. An line (Peleg) causes fusion cells.Virology. 1975; 64: 367-377Crossref (167) Another ISV, Eilat (EILV), titers delay replication vitro. When were EILV, dissemination delayed heterologous interference mechanism [33.Nasar F. al.Eilat homologous interference.Am. J. Hyg. 2015; 93: 226Google Co-infection ISVs CFAV co-infection [34.Schultz M.J. al.Dual specific limits 518: 406-413Crossref (46) another discovered [35.Vasilakis N. al.Negevirus: taxon wide geographic distribution.J. Virol. 87: 2475-2488Crossref (121) cells, Mayaro [36.Patterson E.I. al.Negeviruses alphaviruses during coinfection.J. 95e0043321Crossref (2) All suggest arboviruses superinfection exclusion, needs further testing population. producing immunomodulatory molecules (termed paratransgenesis) 1C,D). After engineered, it reintroduced arthropod its There requirements candidate symbiont. First, should able stably horizontally maintain long enough [37.Wilke A.B. Marrelli M.T. Paratransgenesis: strategy control.Parasit. Vectors. 342Crossref (97) Second, easily culturable manipulatable, while reducing fitness [38.Lovett B. al.Transgenic rapidly malaria-endemic region Burkina Faso.Science. 364: 894-897Crossref (40) Third, target [39.Wang al.Driving bacteria.Science. 2017; 357: 1399-1402Crossref (116) several candidates shown attributes paratransgenesis (AS1), isolated ovaries, horizontally, facilitating Furthermore, Together, suggests bogorensis populate larval adult organs [40.Favia al.Bacteria genus associate stephensi, Asian malarial vector.Proc. Natl. Acad. 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

Language: Английский

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Next-generation CRISPR gene-drive systems using Cas12a nuclease

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 12, 2023

One method for reducing the impact of vector-borne diseases is through use CRISPR-based gene drives, which manipulate insect populations due to their ability rapidly propagate desired genetic traits into a target population. However, all current drives employ Cas9 nuclease that constitutively active, impeding our control over propagation abilities and limiting generation alternative drive arrangements. Yet, other nucleases such as temperature sensitive Cas12a have not been explored designs in insects. To address this, we herein present proof-of-concept gene-drive system driven by can be regulated via modulation. Furthermore, combined build double capable simultaneously spreading two independent engineered alleles. The development Cas12a-mediated provides an innovative option designing next-generation vector strategies combat disease vectors agricultural pests.

Language: Английский

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Considerations for first field trials of low-threshold gene drive for malaria vector control

Malaria Journal, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 21, 2024

Sustainable reductions in African malaria transmission require innovative tools for mosquito control. One proposal involves the use of low-threshold gene drive Anopheles vector species, where a 'causal pathway' would be initiated by (i) release system target leading to (ii) its subsequent generations, (iii) increase frequency and spread populations, (iv) simultaneous propagation linked genetic trait aimed at reducing vectorial capacity Plasmodium, (v) reduced parasites populations as reaches fixation causing (vi) decreased incidence prevalence. Here scope, objectives, trial design elements, approaches monitoring initial field releases such dive systems are considered, informed successful implementation trials biological control agents, well other tools, including insecticides, Wolbachia, larvicides, attractive-toxic sugar bait systems. Specific research questions addressed identified, adaptive is explored potentially constructive flexible approach facilitate testing causal pathway. A fundamental question decision-makers first will whether there should selective focus on earlier points pathway, efficacy via measurement or wider interrogation entire pathway entomological epidemiological efficacy. How when eventually assessed an essential consideration before decisions any protocols finalized implemented, regardless exclusively efficacy, broader aspects Statistical modelling currently under active development inform design, locations, endpoints. Collectively, considerations here advance realization developer ambitions within next 5 years.

Language: Английский

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Review of gene drive modelling and implications for risk assessment of gene drive organisms

Ecological Modelling, Journal Year: 2023, Volume and Issue: 478, P. 110285 - 110285

Published: Jan. 25, 2023

Synthetic gene drive (GD) systems constitute a form of novel invasive environmental biotechnology with far-reaching consequences beyond those other known genetically modified organisms (GMOs). During the last 10 years, development GD has been closely linked to mathematical modelling which can provide feedback on how achieve spread but also may be used predict ecological release. GMOs, thus systems, need pass an risk assessment (ERA) prior release into environment. Models in this respect play important role because organisms, even at small scale, not reversible. In our review, we analyse scope and structure existing models examine they assist ERA. Our analysis reveals that majority so far are deterministic, non-spatial tailored for specific target organism. often use simplified assumptions biology species seem made test effectiveness drive. Few go verify whether model predictions realistic under field conditions. We identified four advanced judged most ecologically compared implemented parameters ERA requirements by European Food Safety Authority (EFSA) World Health Organization (WHO) insects mosquitoes. Although number abiotic biotic factors already considered these models, mating-related traits relevant interactions between GMO largely excluded. Overall, results show biological realism still poorly realized current aim efficacy rather than effects. Given complexity natural ecosystems, it possible compile single cover all complexities. Thus, should further developed purpose questions related GDs. Moreover, uncertainty will key issue any RA see improve aspect when drives.

Language: Английский

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Gene Editing and Genetic Control of Hemipteran Pests: Progress, Challenges and Perspectives

Frontiers in Bioengineering and Biotechnology, Journal Year: 2022, Volume and Issue: 10

Published: June 7, 2022

The origin of the order Hemiptera can be traced to late Permian Period more than 230 MYA, well before flowering plants 100 MY later in during Cretaceous period. Hemipteran species consume their liquid diets using a sucking proboscis; for phytophagous hemipterans mouthparts (stylets) are elegant structures that enable voracious feeding from plant xylem or phloem. This adaptation has resulted some hemipteran becoming globally significant pests agriculture resulting annual crop losses. Due reliance on chemical insecticides control insect agricultural settings, many have evolved resistance an urgent need develop new, species-specific and environmentally friendly methods pest control. rapid advances CRISPR/Cas9 technologies model insects such as Drosophila melanogaster , Tribolium castaneum Bombyx mori, Aedes aegypti spurred new round innovative genetic strategies Diptera Lepidoptera increased interest assessing Hemiptera. Genetic approaches have, date, been largely overlooked due problems introducing material into germline these insects. high frequency CRISPR-mediated mutagenesis suggest that, if delivery problem could solved, then gene editing might quickly achieved. Significant realized nine over past 4 years. Here we review progress discuss challenges opportunities extending contemporary this agriculturally important r.

Language: Английский

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Direct and indirect impacts of synthetic biology on biodiversity conservation

iScience, Journal Year: 2022, Volume and Issue: 25(11), P. 105423 - 105423

Published: Oct. 20, 2022

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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Risk management recommendations for environmental releases of gene drive modified insects

Biotechnology Advances, Journal Year: 2021, Volume and Issue: 54, P. 107807 - 107807

Published: July 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.

Language: Английский

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Simulations Reveal High Efficiency and Confinement of a Population Suppression CRISPR Toxin-Antidote Gene Drive

ACS Synthetic Biology, Journal Year: 2023, Volume and Issue: 12(3), P. 809 - 819

Published: Feb. 24, 2023

Though engineered gene drives hold great promise for spreading through and suppressing populations of disease vectors or invasive species, complications such as resistance alleles spatial population structure can prevent their success. Additionally, most forms suppression drives, homing driving Y chromosomes, will generally spread uncontrollably between with even small levels migration. The previously proposed CRISPR-based toxin-antidote system called dominant embryo (TADE) drive could potentially address the issues confinement resistance. However, it is a relatively weak form compared to which might make particularly vulnerable structure. In this study, we investigate TADE using individual-based simulations in continuous landscape. We find that actually more confined than simple models without space, its efficient low cleavage rate embryos from maternally deposited Cas9. Furthermore, performed well space scenarios if initial release requirements were met, timely manner being severely affected by chasing, phenomenon wild-type individuals avoid recolonizing empty areas. At higher cut rates, loses ability spread, but single, widespread often still induce rapid collapse. Thus, be successfully constructed, they may play an important role control species when stringent target desired.

Language: Английский

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Gene drive designs for efficient and localisable population suppression using Y-linked editors

PLoS Genetics, Journal Year: 2022, Volume and Issue: 18(12), P. e1010550 - e1010550

Published: Dec. 27, 2022

The sterile insect technique (SIT) has been successful in controlling some pest species but is not practicable for many others due to the large number of individuals that need be reared and released. Previous computer modelling demonstrated release males carrying a Y-linked editor kills or sterilises female descendants could orders magnitude more efficient than SIT while still remaining spatially restricted, particularly if combined with an autosomal sex distorter. In principle, further gains efficiency achieved by using self-propagating double drive design, which each two components (the ratio distorter) boosted transmission other. To better understand expected dynamics impact releasing constructs this new design we have analysed deterministic population genetic dynamic model. Our demonstrates can suppress from very low rates, no invasion threshold. Importantly, work even homing rates are chromosomes silenced at meiosis, potentially expanding range amenable such control. Moreover, predicted impacts exquisitely sensitive relatively small (e.g., 25%) changes allele frequencies target population, exploited sequence-based targeting. Analysis published Anopheles gambiae genome sequences indicates weakly differentiated populations F ST 0.02 there may thousands suitably genomic sites used restrict spread release. proposed extends already promising development pathway based on editors, therefore useful addition menu options biocontrol.

Language: Английский

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