Curing mosquitoes with genetic approaches for malaria control

Trends in Parasitology, Journal Year: 2024, Volume and Issue: 40(6), P. 487 - 499

Published: May 16, 2024

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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Characterization of lab-based swarms of Anopheles gambiae mosquitoes using 3D-video tracking

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: May 30, 2023

Mosquito copulation is a crucial determinant of its capacity to transmit malaria-causing Plasmodium parasites as well underpinning several highly-anticipated vector control methodologies such gene drive and sterile insect technique. For the anopheline mosquitoes responsible for African malaria transmission, mating takes place within crepuscular male swarms which females enter solely mate. However, mechanisms that regulate swarm structure or govern mate choice remain opaque. We used 3D-video tracking approaches computer vision algorithms developed study other complex biological systems document swarming behavior lab-adapted Anopheles gambiae line in lab-based setting. By reconstructing trajectories individual lasting up 15.88 s, containing upwards 200 participants, we documented swarm-like both males females. In single sex swarms, encounters between individuals were fleeting (< 0.75 s). contrast, mixed able detect 79 'brief encounters' (> s; < 2.5 s) 17 longer-lived also examples apparent male-male competition. These findings represent first steps towards more detailed quantitative description courtship one most important vectors malaria.

Language: Английский

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Problem formulation for a small-scale field study of non-gene drive, genetically modified, male bias mosquitoes in Burkina Faso

Human and Ecological Risk Assessment An International Journal, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 39

Published: April 2, 2025

Language: Английский

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The Perpetual Vector Mosquito Threat and Its Eco-Friendly Nemeses

Biology, Journal Year: 2024, Volume and Issue: 13(3), P. 182 - 182

Published: March 12, 2024

Mosquitoes are the most notorious arthropod vectors of viral and parasitic diseases for which approximately half world’s population, ~4,000,000,000, is at risk. Integrated pest management programs (IPMPs) have achieved some success in mitigating regional transmission persistence these diseases. However, as many vector-borne remain pervasive, it obvious that IPMP successes not been absolute eradicating threat imposed by mosquitoes. Moreover, expanding mosquito geographic ranges caused factors related to climate change globalization (travel, trade, migration), evolution resistance synthetic pesticides, present ongoing challenges reducing or eliminating local global burden diseases, especially economically medically disadvantaged societies. Abatement strategies include control vector populations with pesticides eco-friendly technologies. These “green” technologies SIT, IIT, RIDL, CRISPR/Cas9 gene drive, biological specifically targets aquatic larval stages Regarding latter, effective continues be widespread use Lysinibacillus sphaericus (Ls) Bacillus thuringiensis subsp. israelensis (Bti). Here, we a review health issues elicited mosquitoes, strategies, lastly, focus on biology Ls Bti, an emphasis no has observed field.

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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The Phyloperiodic Approach Removes the “Cryptic Species” and Puts forward Multilevel Organismal Diversity

Diversity, Journal Year: 2024, Volume and Issue: 16(4), P. 220 - 220

Published: April 6, 2024

The notion of the “cryptic species” has recently become an important agenda in biodiversity research. In this study, we show, by applying a periodic-like morphological and molecular framework to nudibranch genus Cadlina from world’s least explored locations Kuril Islands northwestern Pacific, including description six new species, that term should be removed research terminology. We explicitly show different species complex have various degrees phylogenetic distances distinctness, revealing truly multilevel system fine-scale differences similarities. Therefore, designate any these as “cryptic” or “non-cryptic” would completely arbitrary, non-operational, generally meaningless. By this, finally strongly propose remove “crypticity” (in sense “indistinguishable species”) arsenal modern biology, phylogeny taxonomy. importance differentiation is shown for addressing conservation global warming challenges. Six are named after scientists who not always received honours they deserve, two women did receive their respective Nobel Prizes.

Language: Английский

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Genetic and geographic population structure in the malaria vector, Anopheles farauti, provides a candidate system for pioneering confinable gene-drive releases

Heredity, Journal Year: 2024, Volume and Issue: 132(5), P. 232 - 246

Published: March 18, 2024

Abstract Indoor insecticide applications are the primary tool for reducing malaria transmission in Solomon Archipelago, a region where Anopheles farauti is only common vector. Due to evolution of behavioural resistance some An . populations, these have become less effective. New control interventions therefore needed this region, and gene-drives provide promising new technology. In considering developing population-specific (local) gene-drive An. , we detail species’ population genetic structure using microsatellites whole mitogenomes, finding many spatially confined populations both within between landmasses. This strong suggests that would be useful system population-specific, confinable field release, private alleles can used as Cas9 targets. Previous work on gambiae has Cardinal gene development global replacement gene-drive. We also analyse assess whether it may suitable target engineer modification local populations. Despite extensive observed microsatellites, one remote island from Vanuatu contained fixed at locus. Nonetheless, study provides an initial framework further genomic investigations discover high-frequency allele targets localized enable strains modifying localised with minimal chance escape low-risk route trial evaluations.

Language: Английский

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Requirements for market entry of gene drive-modified mosquitoes for control of vector-borne diseases: analogies to other biologic and biotechnology products

Frontiers in Bioengineering and Biotechnology, Journal Year: 2023, Volume and Issue: 11

Published: June 8, 2023

Gene drive-modified mosquitoes (GDMMs) are proposed as new tools for control and elimination of malaria other mosquito-borne diseases, promising results have been observed from testing conducted in containment. Although still at an early stage development, it is important to begin now consider approval procedures market entry strategies the eventual implementation GDMMs context disease programs, these could impact future research plans. It expected that, types products, those seeking bring will be required provide sufficient information allow regulator(s) determine whether product safe effective its use. There already has much emphasis on developing requirements biosafety components "safe effective" benchmark, largely concerned with their regulation genetically modified organisms. Other potential received little attention, however. implemented primarily public health any regulatory analogies such pharmaceuticals, vaccines, or chemical pesticides, must take into account characteristics live mosquito products. Typical manufacturing standards related identity, potency quality need adapted GDMMs. Valuable lessons can drawn processes whole organism (GM) Supply chain requirements, scale production, location design production facilities, methods distribution delivery, dependent upon particular GDMM product, conditions use, region served. Plans fulfilling supply needs build experience development insect products use agriculture. Implementation would benefit additional enabling technologies long-term storage life stages, efficient mass area-wide delivery Early consideration practical help mitigate downstream delays technologies.

Language: Английский

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Bioinformatic and literature assessment of toxicity and allergenicity of a CRISPR-Cas9 engineered gene drive to control Anopheles gambiae the mosquito vector of human malaria

Malaria Journal, Journal Year: 2023, Volume and Issue: 22(1)

Published: Aug. 14, 2023

Population suppression gene drive is currently being evaluated, including via environmental risk assessment (ERA), for malaria vector control. One such involves the dsxFCRISPRh transgene encoding (i) hCas9 endonuclease, (ii) T1 guide RNA (gRNA) targeting doublesex locus, and (iii) DsRed fluorescent marker protein, in genetically-modified mosquitoes (GMMs). Problem formulation, first stage of ERA, releases previously identified nine potential harms to environment or health that could occur, should expressed products cause allergenicity toxicity.Amino acid sequences were interrogated against those toxins allergens from NCBI, UniProt, COMPARE AllergenOnline bioinformatic databases gRNA was compared with microRNAs miRBase database impacts on expression associated toxicity allergenicity. PubMed also searched any evidence Cas9 DsRed, donor organisms which these originally derived.While nuclease activity can be toxic some cell types vitro found share homology prokaryotic toxin VapC, there no previous studies a humans other animals hCas9. Although did contain an 8-mer epitope latex allergen Hev b 9, full amino sequence not homologous known allergens. Combined lack literature allergenicity, this indicated negligible No matches between either Anopheles humans. Moreover, exposure transgenic proteins assessed as negligible.Bioinformatic assessments convincing suggest toxins, indicating population control result increased animals. These results inform evaluations GMMs developed vivo clinical applications CRISPR-Cas9.

Language: Английский

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