siRNA treatment of diseases or conditions related to levels of IKK-gamma

• US 7,022,828 B2
• Filed: 05/28/2002
• Issued: 04/04/2006
• Est. Priority Date: 04/05/2001
• Status: Expired due to Fees

• Current Assignee: Sirna Therapeutics, Inc. (Alnylam Pharmaceuticals Incorporated)
• Original Assignee: Sirna Therapeutics, Inc. (Alnylam Pharmaceuticals Incorporated)
• Inventors: McSwiggen, James A.
• Primary Examiner(s): Martinell, James
• Application Number:
  US10/156,306
• Publication Number:
  US 20030119017A1
• Time in Patent Office: 1,407 Days
• Field of Search: 514/44, 536/23.1, 536/23.5
• US Class Current: 536/23.1
• 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: 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 15/1137 against enzymes viral enzymes C12N15/1131; receptors C12N15/1138
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/12 catalytic nucleic acids, e.g. ribozymes
• CPC Class Codes: C12N 2310/121 Hammerhead
• CPC Class Codes: C12N 2310/13 Decoys
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/18 acting by a non-sequence specific mechanism other than C12N2310/16 or C12N2310/17
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/317 with an inverted bond, e.g. a cap structure
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/332 Abasic residue
• CPC Class Codes: C12N 2310/346 having a combination of backbone and sugar modifications
• CPC Class Codes: C12N 2310/3521 Methyl

Abstract

The present invention relates to nucleic acid molecules, including antisense and enzymatic nucleic acid molecules, such as hammerhead ribozymes, DNAzymes, allozymes, aptamers, decoys and siRNA (RNAi), which modulate the expression or function of IKK genes, such as IKK-gamma, IKK-alpha, or IKK-beta, and PKR genes.

Claims

1. A chemically modified double stranded siRNA molecule that down regulates expression of an IKK-gamma gene via RNA interference (RNAi), wherein:

a) each strand of said siRNA molecule is independently about 18 to about 28 nucleotides in length; and

b) one strand of said siRNA molecule comprises nucleotide sequence having sufficient complementarity to an RNA of said IKK-gamma gene for the siRNA molecule to direct cleavage of said RNA via RNA interference.

2. The siRNA molecule of claim 1, wherein each strand of the siRNA molecule comprises about 18 to about 28 nucleotides, and wherein each strand comprises at least about 14 to 24 nucleotides that are complementary to the nucleotides of the other strand.

3. The siRNA molecule of claim 1, wherein said siNA molecule is assembled from two separate oligonucleotide fragments wherein a first fragment comprises the sense strand and a second fragment comprises the antisense strand of said siNA molecule.

4. The siRNA molecule of claim 3, wherein said sense strand is connected to the antisense strand via a linker molecule.

5. The siRNA molecule of claim 4, wherein said linker molecule is a polynucleotide linker.

6. The siRNA molecule of claim 4, wherein said linker molecule is a non-nucleotide linker.

7. The siRNA molecule of claim 3, wherein said second fragment comprises a terminal cap moiety at a 5′

-end, a 3′

-end, or both of the 5′ and

3′

ends of said second strand.

8. The siRNA molecule of claim 7, wherein said terminal cap moiety is an inverted deoxy abasic moiety.

9. The siRNA molecule of claim 3, wherein said first fragment comprises a phosphorothioate internucleotide linkage at the 3′

end of said first strand.

10. The siRNA molecule of claim 1, wherein said siRNA molecule comprises at least one 2′

-sugar modification.

11. The siRNA molecule of claim 10, wherein said 2′

-sugar modification is a 2′

-deoxy-2′

-fluoro modification.

12. The siRNA molecule of claim 10, wherein said 2′

-sugar modification is a 2′

-O-methyl modification.

13. The siRNA molecule of claim 10, wherein said 2′

-sugar modification is a 2′

-deoxy modification.

14. The siRNA molecule of claim 1, wherein said siRNA molecule comprises at least one nucleic acid base modification.

15. The siRNA molecule of claim 1, wherein said siRNA molecule comprises at least one phosphate backbone modification.

16. A composition comprising the siRNA molecule of claim 1 in a pharmaceutically acceptable carrier or diluent.