Disruption of dengue virus transmission by mosquitoes

Franz, Alexander W. E.; Balaraman, Velmurugan; Fraser, Malcolm J.

doi:10.1016/j.cois.2014.12.009

Cited by 9 publications

(6 citation statements)

References 81 publications

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“…Combined with a gene drive, they could provide a promising new approach to fight this devastating disease. Other proposed applications range from spreading genetically engineered antiviral effector genes against dengue [ 18 ], to suppressing the populations of invasive crop pests such as Drosophila suzukii [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Novel CRISPR/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations

et al. 2017

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A functioning gene drive system could fundamentally change our strategies for the control of vector-borne diseases by facilitating rapid dissemination of transgenes that prevent pathogen transmission or reduce vector capacity. CRISPR/Cas9 gene drive promises such a mechanism, which works by converting cells that are heterozygous for the drive construct into homozygotes, thereby enabling super-Mendelian inheritance. Although CRISPR gene drive activity has already been demonstrated, a key obstacle for current systems is their propensity to generate resistance alleles, which cannot be converted to drive alleles. In this study, we developed two CRISPR gene drive constructs based on the nanos and vasa promoters that allowed us to illuminate the different mechanisms by which resistance alleles are formed in the model organism Drosophila melanogaster. We observed resistance allele formation at high rates both prior to fertilization in the germline and post-fertilization in the embryo due to maternally deposited Cas9. Assessment of drive activity in genetically diverse backgrounds further revealed substantial differences in conversion efficiency and resistance rates. Our results demonstrate that the evolution of resistance will likely impose a severe limitation to the effectiveness of current CRISPR gene drive approaches, especially when applied to diverse natural populations.

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Section: Introductionmentioning

confidence: 99%

Novel CRISPR/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations

et al. 2017

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“…Thus, strategies to reduce infection incidence must rely on the control of its mosquito vector, principally Aedes aegypti [ 3 , 4 ]. While permanent eradication is unlikely to be achieved, many emerging genetic and biological approaches aim to reduce mosquito vectorial capacity [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Costs of Three Wolbachia Infections on the Survival of Aedes aegypti Larvae under Starvation Conditions

2016

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The mosquito Aedes aegypti, the principal vector of dengue virus, has recently been infected experimentally with Wolbachia: intracellular bacteria that possess potential as dengue biological control agents. Wolbachia depend on their hosts for nutrients they are unable to synthesize themselves. Consequently, competition between Wolbachia and their host for resources could reduce host fitness under the competitive conditions commonly experienced by larvae of Ae. aegypti in the field, hampering the invasion of Wolbachia into natural mosquito populations. We assess the survival and development of Ae. aegypti larvae under starvation conditions when infected with each of three experimentally-generated Wolbachia strains: wMel, wMelPop and wAlbB, and compare their fitness to wild-type uninfected larvae. We find that all three Wolbachia infections reduce the survival of larvae relative to those that are uninfected, and the severity of the effect is concordant with previously characterized fitness costs to other life stages. We also investigate the ability of larvae to recover from extended food deprivation and find no effect of Wolbachia on this trait. Aedes aegypti larvae of all infection types were able to resume their development after one month of no food, pupate rapidly, emerge at a large size, and exhibit complete cytoplasmic incompatibility and maternal transmission. A lowered ability of Wolbachia-infected larvae to survive under starvation conditions will increase the threshold infection frequency required for Wolbachia to establish in highly competitive natural Ae. aegypti populations and will also reduce the speed of invasion. This study also provides insights into survival strategies of larvae when developing in stressful environments.

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“…Considerable progress has been made in assessing payload genes for the reduction of malaria transmission by mosquitoes 140,141 , some of the most promising of which are an AKT transgene expressed in the midgut 142 and a single-chain antibody expressed in the salivary gland 143 . Dengue-refractory mosquitoes have also been engineered 144,145 , but these only confer resistance to dengue-2, which is just one of five known serotypes. It may be possible to develop mosquitoes that are refractory to all dengue serotypes by using an RNA-guided endonuclease with specific guide RNAs targeting the RNA genome of each serotype, but this remains to be demonstrated.…”

Section: Box 1 | Applications Of Gene Drivesmentioning

confidence: 99%

Cheating evolution: engineering gene drives to manipulate the fate of wild populations

2016

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Engineered gene drives - the process of stimulating the biased inheritance of specific genes - have the potential to enable the spread of desirable genes throughout wild populations or to suppress harmful species, and may be particularly useful for the control of vector-borne diseases such as malaria. Although several types of selfish genetic elements exist in nature, few have been successfully engineered in the laboratory thus far. With the discovery of RNA-guided CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR-associated 9) nucleases, which can be utilized to create, streamline and improve synthetic gene drives, this is rapidly changing. Here, we discuss the different types of engineered gene drives and their potential applications, as well as current policies regarding the safety and regulation of gene drives for the manipulation of wild populations.

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Disruption of dengue virus transmission by mosquitoes

Cited by 9 publications

References 81 publications

Novel CRISPR/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations

Novel CRISPR/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations

Costs of Three Wolbachia Infections on the Survival of Aedes aegypti Larvae under Starvation Conditions

Cheating evolution: engineering gene drives to manipulate the fate of wild populations

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