Engineered Antiviral Sensor Targets Infected Mosquitoes

Benetta, Elena Dalla; López-Denman, Adam J.; Li, Hsing-Han; Masri, Reem A.; Brogan, Daniel J.; Bui, Michelle; Yang, Ting; Li, Ming; Dunn, Michael; Klein, Melissa J.; Jackson, Sarah; Catalan, Kyle; Blasdell, Kim R.; Tng, Priscilla; Antoshechkin, Igor; Alphey, Luke; Paradkar, Prasad N.; Akbari, Omar S.

doi:10.1101/2023.01.27.525922

Cited by 7 publications

(1 citation statement)

References 32 publications

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“…To generate a rapid assay for transgene detection that could be used alongside future pgSIT field trials, we adapted the sensitive enzymatic nucleic acid sequence reporter (SENSR) (Brogan et al, 2021a) to rapidly detect pgSIT DNA fragments in Cas9 and gRNA dsx,ix, β Tub constructs in mosquitoes. In SENSR, the presence of transgenic sequences triggers the activation of the Ruminococcus flavefaciens CasRx/gRNA collateral activity that cleaves a quenched probe, resulting in a rapid fluorescent readout (Brogan et al, 2021b; Dalla Benetta et al, 2023) (Brogan et al, 2021a). Multiple ratios of trans-hemizygous pgSIT to WT mosquitoes - 0:1; 1:1; 1:5; 1:10; 1:25; 1:50 and a no template control (NTC) were used to challenge SENSR.…”

Section: Resultsmentioning

confidence: 99%

Targeting Sex Determination to Suppress Mosquito Populations

Kandul

Sun

et al. 2023

Preprint

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Each year, hundreds of millions of people are infected with arboviruses such as dengue, yellow fever, chikungunya, and Zika, which are all primarily spread by the notorious mosquito Aedes aegypti. Traditional control measures have proven insufficient, necessitating innovations. In response, here we generate a next generation CRISPR-based precision-guided sterile insect technique (pgSIT) for Aedes aegypti that disrupts genes essential for sex determination and fertility, producing predominantly sterile males that can be deployed at any life stage. Using mathematical models and empirical testing, we demonstrate that released pgSIT males can effectively compete with, suppress, and eliminate caged mosquito populations. This versatile species-specific platform has the potential for field deployment to control wild populations, safely curtailing disease transmission.

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Section: Resultsmentioning

confidence: 99%

Targeting Sex Determination to Suppress Mosquito Populations

Kandul

Sun

et al. 2023

Preprint

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CRISPR-based gene drives generate super-Mendelian inheritance in the disease vector Culex quinquefasciatus

Harvey-Samuel,

Feng,

Okamoto

et al. 2023

Nat Commun

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Culex mosquitoes pose a significant public health threat as vectors for a variety of diseases including West Nile virus and lymphatic filariasis, and transmit pathogens threatening livestock, companion animals, and endangered birds. Rampant insecticide resistance makes controlling these mosquitoes challenging and necessitates the development of new control strategies. Gene drive technologies have made significant progress in other mosquito species, although similar advances have been lagging in Culex. Here we test a CRISPR-based homing gene drive for Culex quinquefasciatus, and show that the inheritance of two split-gene-drive transgenes, targeting different loci, are biased in the presence of a Cas9-expressing transgene although with modest efficiencies. Our findings extend the list of disease vectors where engineered homing gene drives have been demonstrated to include Culex alongside Anopheles and Aedes, and pave the way for future development of these technologies to control Culex mosquitoes.

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CRISPR-based gene drives generate super-Mendelian inheritance in the disease vectorCulex quinquefasciatus

Harvey-Samuel,

Feng,

Okamoto

et al. 2023

Preprint

View full text Add to dashboard Cite

Culexmosquitoes pose a significant public health threat as vectors for a variety of diseases including West Nile virus and lymphatic filariasis, and transmit pathogens threatening livestock, companion animals, and endangered birds. Rampant insecticide resistance makes controlling these mosquitoes challenging and necessitates the development of new control strategies. Gene drive technologies have made significant progress in other mosquito species, although similar advances have been lagging inCulex. Here we test the first CRISPR-based homing gene drive forCulex quinquefasciatus, demonstrating the possibility of using this technology to controlCulexmosquitoes. Our results show that the inheritance of two split-gene-drive transgenes, targeting different loci, are biased in the presence of a Cas9-expressing transgene although with modest efficiencies. Our findings extend the list of disease vectors where engineered homing gene drives have been demonstrated to includeCulexalongsideAnophelesandAedes, and pave the way for future development of these technologies to controlCulexmosquitoes.

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Engineered Antiviral Sensor Targets Infected Mosquitoes

Cited by 7 publications

References 32 publications

Targeting Sex Determination to Suppress Mosquito Populations

Targeting Sex Determination to Suppress Mosquito Populations

CRISPR-based gene drives generate super-Mendelian inheritance in the disease vector Culex quinquefasciatus

CRISPR-based gene drives generate super-Mendelian inheritance in the disease vectorCulex quinquefasciatus

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