RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA)
This invention relates to compounds, compositions, and methods useful for modulating VEGF and/or VEGFR gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of VEGF and/or VEGFR gene expression and/or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features 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 and methods used to modulate the expression of VEGF and/or VEGFR genes. The application also relates to methods of treating diseases and conditions associated with VEGF and/or VEGFR gene expression, such as ocular diseases and conditions, including age related macular degeneration (AMD) and diabetic retinopathy, as well as providing dosing regimens and treatment protocols.
1. A method for the treatment of an ocular disease in a subject comprising contacting the subject via intravitreal injection with a double stranded nucleic acid molecule 21-40 nucleotides in length comprising a first strand having SEQ ID NO: 2742 and a second strand having SEQ ID NO: 2745 under conditions suitable to inhibit the expression of VEGFR1 in the subject, wherein the ocular disease is an angiogenic disease.
2. The method of claim 1 , wherein said ocular disease is age related macular degeneration (AMD).
3. The method of claim 1 , wherein said ocular disease is diabetic retinopathy.
4. The method of claim 1 , wherein said treatment comprises intravitreal injection of said double stranded nucleic acid molecule in a pharmaceutically acceptable carrier or diluent.
5. The method of claim 4 , wherein said injection takes place every 4 weeks.
6. The method of claim 4 , wherein said injection takes place every 6 weeks.
7. The method of claim 4 , wherein said injection takes place every 8 weeks.
8. The method of claim 4 , wherein said injection takes place every 10 weeks.
9. A method for the treatment of ocular disease in a subject comprising contacting the subject with a double stranded nucleic acid molecule 21-40 nucleotides in length comprising a first strand having SEQ ID NO: 2742 and a second strand having SEQ ID NO: 2745, wherein the treatment comprises administration of the double stranded nucleic acid molecule via periocular injection to an eye of the subject, wherein the ocular disease is an angiogenic disease.
10. The method of claim 9 , wherein said ocular disease is age related macular degeneration (AMD).
11. The method of claim 9 , wherein said ocular disease is diabetic retinopathy.
12. The method of claim 9 , wherein the double stranded nucleic acid molecule is in a pharmaceutically acceptable carrier or diluent.
13. The method of claim 9 , wherein said administration takes place every 4 weeks.
14. The method of claim 9 , wherein said administration takes place every 6 weeks.
15. The method of claim 9 , wherein said administration takes place every 8 weeks.
16. The method of claim 9 , wherein said administration takes place every 10 weeks.