Targeted mosquitocidal toxins
Inventors
Kearney, Christopher Michel • Pruett, Grace
Assignees
Publication Number
US-11479583-B2
Publication Date
2022-10-25
Expiration Date
2038-04-03
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Abstract
Insecticidal toxins described herein are fused toxin peptides made up of a targeting domain fused to a toxin domain. The targeting peptide generates a specific association with mosquitoes by causing the fused toxin peptide to bind mosquitoes in a way that leads to the insecticidal activity. Transgenic plants described herein are mosquitocidal by expressing an insecticidal toxin protein in nectar that includes a targeting peptide to ensure specificity against mosquitoes. These transgenic plants serve as role models for safety, since they are non-crop plants and specific to one mosquito species.
Core Innovation
The present disclosure pertains to targeted insecticidal proteins that are toxic to mosquitoes but not to non-target insect species. The core invention involves fused toxin peptides composed of a mosquito-specific targeting domain fused to a toxin domain. The targeting peptide facilitates a specific association with mosquitoes by enabling the fused toxin peptide to bind in a way that activates the toxin’s mosquitocidal activity. Expression of these fused toxin peptides in transgenic plants, particularly in the nectar, allows for a targeted and ecological approach to mosquito control.
This innovation addresses the long-standing problem of mosquito control, which is compounded by limited vaccine development, emergence of new mosquito-borne pathogens, and the failure or harmful side effects of traditional control measures such as wide-scale insecticide spraying. Current approaches often harm non-target species, including beneficial insects like honeybees, and are ecologically disruptive. There is a need for a mosquito control method that is both effective and highly specific to mosquitoes, without adversely impacting other insects or the environment.
The described fusion peptides can be expressed in various organisms (such as E. coli or plants) and can be designed using targeting domains derived from Domain III of mosquito-specific viruses, such as the glycoprotein of dengue virus, to direct mosquito-specific binding. In preferred embodiments, transgenic nectar-producing plants, such as Impatiens walleriana, are engineered to express these fusion peptides specifically in nectar, ensuring uptake and mosquitocidal activity localized to mosquitoes feeding on the plant, while avoiding toxicity to honeybees and other pollinators. This method is characterized as biosafe, cost-effective, scalable, and offers long-term mosquito control.
Claims Coverage
There are four independent inventive features covered by the claims in this patent.
Mosquitocidal toxin with specific targeting and toxicity
A fused toxin peptide comprising: - A mosquito targeting peptide consisting of SEQ ID NO:1 from Domain III of the glycoprotein of dengue virus. - A toxin peptide that is a Hv1a spider toxin peptide. - The mosquito targeting peptide targets Aedes aegypti mosquitoes. - The fused toxin peptide is toxic to Aedes aegypti mosquitoes.
Method for producing a modified plant expressing the mosquitocidal toxin
A method comprising: 1. Expressing a nucleic acid construct encoding the mosquitocidal toxin (as defined above) in target cells of a plant. 2. Producing a modified plant that expresses the fused toxin peptide.
Method for producing a modified plant expressing the fused toxin peptide in nectar
A method comprising: - Expressing a nucleic acid construct encoding the defined mosquitocidal toxin in cells of the plant producing nectar. - The plant is Impatiens walleriana. - Producing a modified plant expressing the fused toxin peptide in the nectar.
Modified mosquitocidal plant expressing the fused toxin peptide
A modified plant that expresses the defined mosquitocidal toxin (fused toxin peptide) in cells of the plant.
The inventive features provide a mosquito-specific peptide toxin, methods for expressing this toxin in plants or specifically in nectar cells—most notably in Impatiens walleriana—and the corresponding transgenic plants themselves, enabling highly targeted control of Aedes aegypti mosquitoes.
Stated Advantages
Provides mosquito control that is highly specific to mosquitoes and not toxic to non-target insect species, including bees and pollinators.
Offers an ecological, biosafe, cost-effective, and long-lived mosquito control strategy by leveraging the mosquito’s critical dependence on nectar.
Prevents environmental harm associated with insecticide spraying and minimizes the risk of affecting beneficial organisms.
The technology is reversible, local, and predictable, allowing control areas to be determined by where the plants are placed and enabling reversal by plant removal.
Engineered plants, such as Impatiens walleriana, are easy to grow, require little maintenance, and can be produced commercially using seeds or cuttings.
Does not involve introduction into the human food chain and can be installed directly by end users.
Can be confined to nectar expression, limiting environmental spread of the transgene and further improving biosafety.
Documented Applications
Use in transgenic plants, especially nectar or ornamental plants, to express mosquito-specific toxins for targeted control of mosquito populations.
Production of fusion peptide toxins in organisms like E. coli or yeast, followed by isolation and formulation for mosquitocidal applications.
Use of modified Impatiens walleriana plants expressing the fused toxin peptide in nectar as a garden-based mosquito control measure.
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