System for the biocontrol of disease-transmitting mosquitoes and their eggs using horizontally transferable symbiotic bacteria to deliver pathogen specific interfering RNA polynucleotides
Inventors
Sayre, Richard • Xu, Jiannong • Borlee, Bradley R. • Lymperopoulos, Konstantinos • Kading, Rebekah • Black, William • Olson, Kenneth • Blair, Carol
Assignees
Pebble Labs Inc • Colorado State University Research Foundation
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Publication Number
US-11396653-B2
Publication Date
2022-07-26
Expiration Date
Abstract
The inventive technology relates to novel paratransgenic strategies for the control of pathogens. The inventive technology may specifically include a novel paratransgenic system configured to deliver one or more inhibitory RNA molecules to pathogen/disease-transmitting organisms. In a preferred embodiment, the invention may include one or more genetically engineered symbiotic bacteria configured to persist throughout the life-cycle of a mosquito and deliver one or more interfering RNA molecules to pathogen/disease-transmitting mosquitoes.
Core Innovation
The invention describes methods that introduce into a mosquito a genetically modified bacteria that colonizes the mosquito and includes a nucleotide sequence operably linked to a promoter. The nucleotide sequence encodes a heterologous dsRNA polynucleotide selected from SEQ ID NO.'s 1, 2, 3, 4, 5 and 8, and expression of the dsRNA polynucleotide within the mosquito inhibits expression of a Zika virus or a Dengue virus present in the mosquito by targeting an essential gene of the virus.
A related aspect generates a genetically modified bacteria that colonizes a mosquito and expresses a heterologous RNA polynucleotide that downregulates expression of at least one Zika virus gene or at least one Dengue virus gene, where the genetically modified bacteria is RNase III deficient. The method includes introducing into the mosquito an effective amount of the RNase III deficient, colonizing genetically modified bacteria, and the nucleotide sequence encoding the heterologous RNA polynucleotide is selected from SEQ ID NO.'s 1, 2, 3, 4, 5 and 8.
The disclosed embodiments are directed to problems in which Zika virus or Dengue virus gene expression occurs in a mosquito, and reducing that viral expression is presented as the functional outcome. The dsRNA or downregulating heterologous RNA polynucleotide is configured to inhibit or downregulate viral gene expression, and the genetically modified bacteria are configured to colonize the mosquito as the expression source.
Claims Coverage
The document provides two independent method claims. Both independent claims share the same core RNA-targeting concept, delivered by colonizing genetically modified bacteria into a mosquito, with the second independent claim adding the RNase III deficient bacterial limitation and additional downregulation framing.
Colonizing genetically modified bacteria expressing promoter-linked dsRNA to inhibit viral essential genes in a mosquito
A method introducing into a mosquito a genetically modified bacteria that colonizes the mosquito, wherein the bacteria includes a nucleotide sequence operably linked to a promoter encoding a heterologous dsRNA polynucleotide selected from SEQ ID NO.'s 1, 2, 3, 4, 5 and 8; wherein expression within the mosquito inhibits expression of the Zika virus or Dengue virus present in the mosquito by inhibiting expression of an essential gene.
RNase III deficient colonizing genetically modified bacteria expressing promoter-linked heterologous RNA to downregulate viral gene expression in a mosquito
A method comprising generating an RNase III deficient genetically modified bacteria that colonizes a mosquito and includes a nucleotide sequence operably linked to a promoter encoding a heterologous RNA polynucleotide that downregulates expression of at least one Zika virus gene or at least one Dengue virus gene, with the nucleotide sequence selected from SEQ ID NO.'s 1, 2, 3, 4, 5 and 8; and introducing into the mosquito an effective amount of the RNase III deficient genetically modified bacteria that colonizes the mosquito and expresses the heterologous RNA polynucleotide.
Across both independent claims, the coverage centers on mosquito-colonizing genetically modified bacteria that express promoter-linked heterologous RNA selected from specified SEQ ID NO.'s, with the first independent claim requiring inhibition of viral expression of an essential gene and the second independent claim requiring an RNase III deficient bacterial system and downregulation of at least one viral gene.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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