Hepatitis C virus ribozymes

• US 6,043,077 A
• Filed: 10/20/1997
• Issued: 03/28/2000
• Est. Priority Date: 02/29/1996
• Status: Expired due to Fees

• Current Assignee: Immusol Incorporated
• Original Assignee: Immusol Incorporated
• Inventors: Tritz, Richard, Barber, Jack R., Yu, Mang, Welch, Peter J., Yei, SoonPin
• Primary Examiner(s): Brusca, John S.
• Assistant Examiner(s): McGarry, Sean
• Application Number:
  US08/954,210
• Time in Patent Office: 890 Days
• Field of Search: 435/6, 435/91.31, 435/320.1, 435/325, 435/366, 435/363, 435/375, 536/23.1, 536/23.2, 536/24.1, 536/24.5, 514/44
• US Class Current: 435/236
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C12N 15/1131 against viruses
• CPC Class Codes: C12N 2310/111 spanning the whole gene, or a large part of it
• CPC Class Codes: C12N 2310/122 Hairpin
• CPC Class Codes: C12N 2799/022 where the vector is derived from an adenovirus
• CPC Class Codes: C12N 2799/025 where the vector is derived from a parvovirus
• CPC Class Codes: C12N 2799/027 where the vector is derived from a retrovirus

Abstract

This invention provides ribozymes useful to treat or prevent Hepatitis C Virus ("HCV") infection or disease in an organism or subject, as well as methods of treating an HCV infection or disease. Reagents such as vectors, host cells, DNA molecules coding for these ribozymes useful in methods of treatment and prevention of HCV infection or disease are also provided.

Claims

1. A ribozyme having the ability to inhibit replication, infectivity, or gene expression of a hepatitis C virus wherein the ribozyme is directed to a target sequence selected from the group consisting of SEQ. ID NO. 38, 39, 40, 41, 42, 43 44, 54, and 65.

2. The ribozyme according to claim 1 wherein said ribozyme is a hairpin ribozyme.

3. A nucleic acid molecule encoding a ribozyme according to claims 1 or 2.

4. The nucleic acid molecule of claim 3 wherein the nucleic acid molecule is DNA.

5. A host cell containing the ribozyme or nucleic acid molecule according to any one of claims 1 or 2.

6. A vector, comprising a promoter operably linked to the nucleic acid molecule according to claim 3.

7. The vector according to claim 6, wherein said promoter is a polIII or CMV promoter.

8. The vector according to claim 6 wherein said vector is a plasmid, a viral vector, retrotransposon or a cosmid.

9. The vector according to claim 6 wherein said viral vector is a recombinant adenoviral or retroviral vector.

10. A host cell containing the vector according to claim 6.

11. A method for producing a ribozyme, the ribozyme being able to inhibit hepatitis C viral infection, replication, or gene expression in a cell, comprising providing DNA encoding a ribozyme according to any one of claims 1 to 2 under the transcriptional control of a promoter, and transcribing the DNA to produce said ribozyme.

12. The method according to claim 11, further comprising the step of purifying the ribozyme.

13. The method according to claim 11 wherein said ribozyme is produced in vitro.

14. The method according to claim 11 wherein said ribozyme is produced in vivo in a cell culture.

15. A method of interfering with hepatitis C virus (HCV) replication or gene expression in a cell infected in a cell culture with HCV, which comprises introducing into the cell an effective amount of the ribozyme according to claims 1 or 2.

16. A vector, comprising a promoter operably linked to the nucleic acid molecule according to claim 4.

17. A method of interfering with hepatitis C virus (HCV) replication or gene expression in a cell infected in a cell culture with HCV, which comprises introducing into the cell an effective amount of a vector according to claims 7 or 16.

18. The method according to claim 15, wherein said cell is a human cell.

19. The method according to claim 17 wherein said vector is a recombinant adenoviral or retroviral vector.

20. A composition, comprising a ribozyme according to claims 1 or 2, in combination with a pharmaceutically acceptable carrier or diluent.

21. A composition, comprising a nucleic acid molecule according to claim 3, in combination with a pharmaceutically acceptable carrier or diluent.

22. A composition, comprising a vector according to any one of claims 6 to 9, in combination with a pharmaceutically acceptable carrier or diluent.

23. A host cell containing the ribozyme or nucleic acid molecule according to claim 3.

24. The method according to claim 14 wherein said cell is a human cell.

25. A composition, comprising a nucleic acid molecule according to claim 4, in combination with a pharmaceutically acceptable carrier or diluent.

26. The vector according to claim 16 wherein said promoter is a polIII or CMV promoter.

27. The vector according to claim 16 wherein said vector is a plasmid, a viral vector, retrotransposon or a cosmid.

28. The vector according to claim 16 wherein said viral vector is a recombinant, adenoviral or retroviral vector.

29. A host cell containing the vector according to claim 16.