Antimalarial drug discovery: progress and approaches

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(10), P. 807 - 826

Published: Aug. 31, 2023

Language: 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, Journal Year: 2022, Volume and Issue: 12(6)

Published: April 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.

Language: Английский

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Burmese pythons in Florida: A synthesis of biology, impacts, and management tools

NeoBiota, Journal Year: 2023, Volume and Issue: 80, P. 1 - 119

Published: Jan. 10, 2023

Burmese pythons ( Python molurus bivittatus ) are native to southeastern Asia, however, there is an established invasive population inhabiting much of southern Florida throughout the Greater Everglades Ecosystem. Pythons have severely impacted species and ecosystems in represent one most intractable invasive-species management issues across globe. The difficulty stems from a unique combination inaccessible habitat cryptic resilient nature that thrive subtropical environment Florida, rendering them extremely challenging detect. Here we provide comprehensive review synthesis science relevant managing pythons. We describe existing control tools challenges productive research, identifying key knowledge gaps would improve future research decision making for python control.

Language: Английский

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Gene drive and genetic sex conversion in the global agricultural pest Ceratitis capitata

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 8, 2024

Homing-based gene drives are recently proposed interventions promising the area-wide, species-specific genetic control of harmful insect populations. Here we characterise a first set in tephritid agricultural pest species, Mediterranean fruit fly Ceratitis capitata (medfly). Our results show that medfly is highly amenable to homing-based drive strategies. By targeting transformer gene, also demonstrate how CRISPR-Cas9 can be coupled sex conversion, whereby females transformed into fertile and harmless XX males. Given this unique malleability determination, modelled couple conversion female sterility found such approaches could effective tolerant resistant allele selection target population. open door for developing strains population suppression related pests by co-targeting reproduction shifting reproductive ratio towards They untapped potential tackle an environmentally friendly economical way.

Language: Английский

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Anti-CRISPR Anopheles mosquitoes inhibit gene drive spread under challenging behavioural conditions in large cages

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 1, 2024

CRISPR-based gene drives have the potential to spread within populations and are considered as promising vector control tools. A doublesex-targeting drive was able suppress laboratory Anopheles mosquito in small large cages, it is for field application. Challenges related field-use of evolving regulatory framework suggest that systems modulate or revert action drives, could be part post-release risk-mitigation plans. In this study, we challenge an AcrIIA4-based anti-drive inhibit age-structured gambiae population under complex feeding behavioural conditions. stochastic model predicts experimentally-observed genotype dynamics medium-sized cages highlights necessity large-sized cage trials. These experiments experimental-modelling demonstrate effectiveness different scenarios, providing further corroboration its use controlling Anopheles.

Language: Английский

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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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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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The potential of gene drives in malaria vector species to control malaria in African environments

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 17, 2024

Gene drives are a promising means of malaria control with the potential to cause sustained reductions in transmission. In real environments, however, their impacts will depend on local ecological and epidemiological factors. We develop data-driven model investigate gene that causes vector population suppression. simulate drive releases sixteen ~ 12,000 km

Language: Английский

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Metal ions in insect reproduction: a crosstalk between reproductive physiology and immunity

Current Opinion in Insect Science, Journal Year: 2022, Volume and Issue: 52, P. 100924 - 100924

Published: April 26, 2022

Most insects exhibit high reproductive capacity, which demands large amounts of energy, including macronutrients and micronutrients. Interestingly, many proteins involved in oogenesis depend on metals ions, particular iron (Fe), zinc (Zn), copper (Cu). Mechanisms by metal ions influence reproduction have been described Drosophila melanogaster, but remain poorly understood hematophagous where blood meals include significant ingestion ions. Moreover, there is evidence that some immunity could dual function both processes. This review highlights the importance non-hematophagous insects. In addition, we discuss how optimize physiological processes using crosstalk between physiology immunity, a double-edge sword allocating their functions to protect insect ensure reproduction.

Language: Английский

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