Methods for inhibiting angiogenesis
Methods for inhibiting angiogenesis using gene therapy are disclosed. Genes encoding PLGF or VEGF-B are delivered to cells e.g., tumor cells, which express VEGF, such that heterodimers of PLGF/VEGF and/or VEGF-B/VEGF are formed within the cells, preferably at a greater ratio than homodimers of VEGF/VEGF. The heterodimers have reduced angiogenic activity compared to VEGF homodimers.
1 . A method of inhibiting angiogenesis comprising delivering a gene encoding a VEGF binding member selected from the group consisting of PLGF and VEGF-B to a cell which expresses VEGF, such that the binding member is co-expressed with VEGF in the cell.
2 . The method of claim 1 , wherein the VEGF binding member is PLGF.
3 . The method of claim 1 , wherein the VEGF binding member forms a heterodimer with VEGF within the cell.
4 . The method of claim 1 , wherein the gene is contained within a vector.
5 . The method of claim 4 , wherein vector is selected from the group consisting of an adenoviral vector, a retroviral vector, a vaccinia virus, an adeno-associated viral vector, an RNA vector, a liposome, a cationic lipid, a lentiviral vector, an Adeno-associated Virus, and a transposon.
6 . The method of claim 1 , wherein the gene is co-administered with another anti-angiogenic agent.
7 . The method of claim 1 , wherein the cell expressing VEGF is a tumor cell.
8 . The method of claim 1 , wherein the gene is delivered to a subject suffering from a disease caused by angiogenesis.
9 . The method of claim 8 , wherein the disease is cancer.
10 . The method of claim 8 , wherein the disease is diabetic retinopathy.
11 . The method of claim 8 , wherein the disease is rheumatoid arthritis.