Combating mosquito-borne diseases using genetic control technologies

Wang, Guan-Hong; Gamez, Stephanie; Raban, Robyn; Marshall, John M.; Alphey, Luke; Li, Ming; Rasgon, Jason L.; Akbari, Omar S.

doi:10.1038/s41467-021-24654-z

Cited by 117 publications

(83 citation statements)

References 109 publications

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“…Open field releases of Wolbachia-infected mosquitoes are becoming one of the best ways to control arbovirus transmission. Wolbachia "population replacement" programs involve the release of mosquitoes carrying a Wolbachia infection that spreads through mosquito populations and reduces their vector competence [1][2][3]. Several different Wolbachia strains from other insects have been introduced into Ae.…”

Section: Introductionmentioning

confidence: 99%

A decade of stability for wMel Wolbachia in natural Aedes aegypti populations

et al. 2022

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Mosquitoes carrying Wolbachia endosymbionts are being released in many countries for arbovirus control. The wMel strain of Wolbachia blocks Aedes-borne virus transmission and can spread throughout mosquito populations by inducing cytoplasmic incompatibility. Aedes aegypti mosquitoes carrying wMel were first released into the field in Cairns, Australia, over a decade ago, and with wider releases have resulted in the near elimination of local dengue transmission. The long-term stability of Wolbachia effects is critical for ongoing disease suppression, requiring tracking of phenotypic and genomic changes in Wolbachia infections following releases. We used a combination of field surveys, phenotypic assessments, and Wolbachia genome sequencing to show that wMel has remained stable in its effects for up to a decade in Australian Ae. aegypti populations. Phenotypic comparisons of wMel-infected and uninfected mosquitoes from near-field and long-term laboratory populations suggest limited changes in the effects of wMel on mosquito fitness. Treating mosquitoes with antibiotics used to cure the wMel infection had limited effects on fitness in the next generation, supporting the use of tetracycline for generating uninfected mosquitoes without off-target effects. wMel has a temporally stable within-host density and continues to induce complete cytoplasmic incompatibility. A comparison of wMel genomes from pre-release (2010) and nine years post-release (2020) populations show few genomic differences and little divergence between release locations, consistent with the lack of phenotypic changes. These results indicate that releases of Wolbachia-infected mosquitoes for population replacement are likely to be effective for many years, but ongoing monitoring remains important to track potential evolutionary changes.

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Section: Introductionmentioning

confidence: 99%

A decade of stability for wMel Wolbachia in natural Aedes aegypti populations

et al. 2022

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“…In addition to increasing access to long-lasting insecticidetreated nets (LLINs) and other currently-available tools such as artemisinin combination therapy drugs (ACTs), it is clear that new tools will be needed to meet Global Technical Strategy milestones for reductions in malaria incidence and mortality, with two of the most promising novel tools currently being malaria vaccines and gene drive-modified mosquitoes. Gene drive approaches bias inheritance in favor of an introduced allele intended to spread through the mosquito population, and fall into two main categories: i) "population suppression," whereby the introduced allele induces a fitness load or sex bias, reducing mosquito numbers, and ii) "population modification," whereby the introduced allele disrupts pathogen transmission, reducing mosquito vector competence (3).…”

Section: Introductionmentioning

confidence: 99%

Target Product Profiles for Mosquito Gene Drives: Incorporating Insights From Mathematical Models

Mondal¹,

Vásquez²,

Marshall³

2022

Front. Trop. Dis

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Mosquito-borne diseases such as malaria continue to pose a major global health burden, and the impact of currently-available interventions is stagnating. Consequently, there is interest in novel tools to control these diseases, including gene drive-modified mosquitoes. As these tools continue to be refined, decisions on whether to implement them in the field depend on their alignment with target product profiles (TPPs) that define product characteristics required to achieve desired entomological and epidemiological outcomes. TPPs are increasingly being used for malaria and vector control interventions, such as attractive targeted sugar baits and long-acting injectable drugs, as they progress through the development pipeline. For mosquito gene drive products, reliable predictions from mathematical models are an essential part of these analyses, as field releases could potentially be irreversible. Here, we review the prior use of mathematical models in developing TPPs for malaria and vector control tools and discuss lessons from these analyses that may apply to mosquito gene drives. We recommend that, as gene drive technology gets closer to field release, discussions regarding target outcomes engage a wide range of stakeholders and account for settings of interest and vector species present. Given the relatively large number of parameters that describe gene drive products, machine learning approaches may be useful to explore parameter space, and an emphasis on conservative fitness estimates is advisable, given the difficulty of accurately measuring these parameters prior to field studies. Modeling may also help to inform the risk, remediation and cost dimensions of mosquito gene drive TPPs.

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“…Mosquitoes are crucial vectors in the epidemiology of numerous human viral diseases, such as dengue, chikungunya, malaria, yellow fever, and the Zika virus disease, all of which provide significant health hazards as well as economic losses worldwide [1][2][3]. Vector biocontrol strategies include the use of entomopathogenic bacteria, such as Bacillus spp.…”

Section: Introductionmentioning

confidence: 99%

Recombinant Mosquito Densovirus with Bti Toxins Significantly Improves Pathogenicity against Aedes albopictus

Batool

Álam

Liu

et al. 2022

Toxins

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Mosquito densoviruses (MDVs) are mosquito-specific viruses that are recommended as mosquito bio-control agents. The MDV Aedes aegypti densovirus (AeDNV) is a good candidate for controlling mosquitoes. However, the slow activity restricts their widespread use for vector control. In this study, we introduced the Bacillus thuringiensis (Bti) toxin Cry11Aa domain II loop α8 and Cyt1Aa loop β6-αE peptides into the AeDNV genome to improve its mosquitocidal efficiency; protein expression was confirmed using nanoscale liquid chromatography coupled to tandem mass spectrometry (nano LC-MS/MS). Recombinant plasmids were transfected into mosquito C6/36 cell lines, and the expression of specific peptides was detected through RT-PCR. A toxicity bioassay against the first instar Aedes albopictus larvae revealed that the pathogenic activity of recombinant AeDNV was significantly higher and faster than the wild-type (wt) viruses, and mortality increased in a dose-dependent manner. The recombinant viruses were genetically stable and displayed growth phenotype and virus proliferation ability, similar to wild-type AeDNV. Our novel results offer further insights by combining two mosquitocidal pathogens to improve viral toxicity for mosquito control.

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Combating mosquito-borne diseases using genetic control technologies

Cited by 117 publications

References 109 publications

A decade of stability for wMel Wolbachia in natural Aedes aegypti populations

A decade of stability for wMel Wolbachia in natural Aedes aegypti populations

Target Product Profiles for Mosquito Gene Drives: Incorporating Insights From Mathematical Models

Recombinant Mosquito Densovirus with Bti Toxins Significantly Improves Pathogenicity against Aedes albopictus

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