RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA)

• US 7,176,304 B2
• Filed: 05/11/2004
• Issued: 02/13/2007
• Est. Priority Date: 02/20/2002
• Status: Expired due to Fees

• Current Assignee: Sirna Therapeutics, Inc. (Alnylam Pharmaceuticals Incorporated)
• Original Assignee: Sirna Therapeutics, Inc. (Alnylam Pharmaceuticals Incorporated)
• Inventors: Beigelman, Leonid, McSwiggen, James, Pavco, Pamela
• Primary Examiner(s): Schultz; James
• Assistant Examiner(s): BOWMAN, AMY HUDSON
• Application Number:
  US10/844,076
• Publication Number:
  US 20050171039A1
• Time in Patent Office: 1,008 Days
• Field of Search: 435/6, 514/44, 536/23.1, 536/24.3, 536/24.31, 536/24.33, 536/24.5
• US Class Current: 536/24.5
• CPC Class Codes: C12N 15/111 General methods applicable to biologically active non-coding nucleic acids
• CPC Class Codes: C12N 15/1136 against growth factors, growth regulators, cytokines, lymphokines or hormones
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/14 interfering N.A.
• 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 2310/322 2'-R Modification
• CPC Class Codes: C12N 2310/3521 Methyl
• CPC Class Codes: C12N 2310/3533 Halogen
• CPC Class Codes: C12N 2310/51 in polymeric form, e.g. multimers, concatemers

Abstract

The present invention concerns methods and reagents useful in modulating vascular endothelial growth factor (VEGF, VEGF-A, VEGF-B, VEGF-C, VEGF-D) and/or vascular endothelial growth factor receptor (e.g., VEGFR1, VEGFR2 and/or VEGFr3) gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against VEGF and/or VEGFr gene expression and/or activity. The small nucleic acid molecules are useful in the diagnosis and treatment of cancer, proliferative diseases, and any other disease or condition that responds to modulation of VEGF and/or VEGFr expression or activity.

Claims

1. A chemically synthesized double stranded short interfering nucleic acid (siNA) molecule that directs cleavage of a vascular endothelial growth factor receptor 1 (VEGER1) RNA via RNA interference (RNAi) wherein:

a. each strand of said siNA molecule is about 21 nucleotides in length;

b. one strand of said siNA molecule comprises a nucleotide sequence having sufficient complementarity to said VEGFR1 RNA for the siNA molecule to direct cleavage of the VEGFR1 RNA via RNA interference; and

c. said siNA comprises SEQ ID NO;

2185 and SEQ ID NO;

2188.

2. A composition comprising the siNA of claim 1 and a pharmaceutically acceptable carrier or diluent.