Combating mosquito-borne diseases using genetic control technologies

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Июль 19, 2021

Abstract Mosquito-borne diseases, such as dengue and malaria, pose significant global health burdens. Unfortunately, current control methods based on insecticides environmental maintenance have fallen short of eliminating the disease burden. Scalable, deployable, genetic-based solutions are sought to reduce transmission risk these diseases. Pathogen-blocking Wolbachia bacteria, or genome engineering-based mosquito strategies including gene drives been developed address problems, both requiring release modified mosquitoes into environment. Here, we review latest developments, notable similarities, critical distinctions between promising technologies discuss their future applications for mosquito-borne control.

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. 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

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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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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A CRISPR endonuclease gene drive reveals distinct mechanisms of inheritance bias

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Ноя. 21, 2022

Abstract CRISPR/Cas gene drives can bias transgene inheritance through different mechanisms. Homing are designed to replace a wild-type allele with copy of drive element on the homologous chromosome. In Aedes aegypti , sex-determining locus is closely linked white gene, which was previously used as target for homing ( w GDe ). Here, an analysis using this linkage we show that in males did not occur by homing, rather increased propagation donor element. We test same transgenes expressing Cas9 germline regulatory elements sds3 bgcn and nup50 . only find even identical -Cas9 transgene. propose DNA repair outcomes may be more context dependent than anticipated other reported may, fact, their

Язык: Английский

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

Ecological Modelling, Год журнала: 2023, Номер 478, С. 110285 - 110285

Опубликована: Янв. 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.

Язык: Английский

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Double drives and private alleles for localised population genetic control

PLoS Genetics, Год журнала: 2021, Номер 17(3), С. e1009333 - e1009333

Опубликована: Март 23, 2021

Synthetic gene drive constructs could, in principle, provide the basis for highly efficient interventions to control disease vectors and other pest species. This efficiency derives part from leveraging natural processes of dispersal flow spread construct its impacts one population another. However, sometimes (for example, with invasive species) only specific populations are need control, on non-target would be undesirable. Many designs use nucleases that recognise cleave genomic sequences, way restrict their exploit sequence differences between target populations. In this paper we propose model a series low threshold double suppression, each consisting two constructs, imposing reproductive load inserted into differentiated locus controlling first. Simple deterministic, discrete-generation computer simulations used assess alternative designs. We find simplest significantly more robust pre-existing cleavage resistance at than single designs, complex incorporating sex ratio distortion can still, even allowing successful when is neutral there up 50% population. Similar also replacement, similar benefits. A analysis CRISPR PAM sites island mainland malaria mosquito Anopheles gambiae indicates differentiation needed our methods work exist nature. Double drives should considered but localised genetic some

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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Engineering drive–selection balance for localized population suppression with neutral dynamics

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(6)

Опубликована: Фев. 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.

Язык: Английский

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