Compositions for conferring tolerance to viral disease in social insects, and the use thereof

• US 8,507,457 B2
• Filed: 12/21/2011
• Issued: 08/13/2013
• Est. Priority Date: 11/07/2007
• Status: Active Grant

• Current Assignee: GreenLight Biosciences, Inc.
• Original Assignee: Beeologics Inc.
• Inventors: Paldi, Nitzan, Yarden, Gal
• Primary Examiner(s): HILL, KEVIN KAI
• Application Number:
  US13/332,430
• Publication Number:
  US 20120108497A1
• Time in Patent Office: 601 Days
• Field of Search: 514/44, 536/23.1, 536/24.1
• US Class Current: 514/44
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 15/1131 against viruses
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2770/22022 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Abstract

Compositions and methods for reducing susceptibility to infectious disease in bees using RNA interference technology, and more particularly, prevention and treatment of viral infections in honeybees such as Israel acute paralysis virus (IAPV) by feeding of pathogen-specific dsRNA. Further, multiple-pathogen specific dsRNA is disclosed.

Claims

1. A bee-ingestible composition comprising an isolated Israel Acute Paralysis Virus-specific dsRNA comprising SEQ ID NO:

33 and an RNA sequence complementary to the entire SEQ ID NO;

33 and bee feed.

2. The bee-ingestible composition of claim 1, wherein said composition is in solid form.

3. The bee-ingestible composition of claim 1, wherein said composition is in liquid form.

4. The bee-ingestible composition of claim 1, wherein said composition comprises protein.

5. The bee-ingestible composition of claim 4, wherein said protein is in the form of pollen and/or soy patties.

6. The bee-ingestible composition of claim 3, wherein said liquid is a sucrose solution.

7. The bee-ingestible composition of claim 3, wherein said liquid is a corn syrup solution.

8. The bee-ingestible composition of claim 3, wherein said liquid further comprises a carbohydrate or sugar supplement.

9. The bee-ingestible composition of claim 1, wherein said dsRNA is selected from the group consisting of siRNA, shRNA and miRNA.

10. The bee ingestible composition of claim 1, wherein said dsRNA is an siRNA.

14. A method for reducing the susceptibility of a honeybee to Israel Acute Paralysis Virus, comprising feeding the bee an effective amount of the bee-ingestible composition of claim 1, thereby reducing the susceptibility of said bee to Israel Acute Paralysis Virus.

15. The method of claim 14, wherein said honeybee is a forager.

16. The method of claim 14, wherein said honeybee is a hive bee.

17. The method of claim 14, wherein said honeybee is a bee of a colony, wherein said feeding reduces the susceptibility of said bee colony to IAPV.

18. The method of claim 14, wherein said bee-ingestible composition is a liquid bee-ingestible composition.

19. The method of claim 14, wherein said bee-ingestible composition is a solid bee-ingestible composition.

20. The method of claim 14, wherein said bee ingestible composition comprises bee feed and an effective amount of a nucleic acid construct comprising a nucleic acid sequence encoding an RNA sequence complementary to the nucleic acid sequence of SEQ ID NO:

33 operably linked to a promoter functional in host cells,

thereby reducing the susceptibility of said bee to IAPV.

11. A nucleic acid agent consisting of a nucleic acid sequence encoding an RNA sequence complementary to the nucleic acid sequence of SEQ ID NO:

33.

12. A nucleic acid construct comprising the nucleic acid agent of claim 11 operably linked to a promoter sequence functional in a host cell.

13. The nucleic acid construct of claim 12, further comprising at least one regulatory element selected from the group consisting of translation leader sequences, introns, enhancers, stem-loop structures, repressor binding sequences, termination sequences, pausing sequences and polyadenylation recognition sequences.