siRNA Inhibition Of Human Antigen R Expression For Treatment of Cancer
DNA dendrimer linked to both a targeting moiety and a siRNA which inhibits expression of Human antigen R (HuR), pharmaceutical compositions comprising the DNA dendrimers and methods of treatment and use employing the DNA dendrimers. Useful siRNA sequences are also disclosed.
1 . A DNA dendrimer linked to a targeting moiety and to a siRNA which inhibits expression of HuR.
2 . The DNA dendrimer according to claim 1 , wherein the siRNA is selected from the group consisting of SEQ ID NO:1/SEQ ID NO:3 and SEQ ID NO:2/SEQ ID NO:4.
3 . The DNA dendrimer according to claim 1 or 2 , wherein the targeting moiety is selected from the group consisting of folate, transferrin, anti-mesothelin antibody, and combinations thereof.
4 . The DNA dendrimer according to claim 3 , wherein the targeting moiety is folate and the siRNA is SEQ ID NO:2/SEQ ID NO:4.
5 . A pharmaceutical composition comprising a DNA dendrimer according to claim 1 and at least one pharmaceutically acceptable excipient.
6 . The pharmaceutical composition according to claim 5 , wherein the targeting moiety is folate and the siRNA is SEQ ID NO:2/SEQ ID NO:4.
7 . The pharmaceutical composition according to claim 5 , which is formulated for injection or infusion.
8 . A method for inhibiting proliferation of tumor cells which overexpress HuR and/or inhibiting growth of a tumor which overexpresses HuR, the method comprising administering to the tumor cells or tumor a composition comprising a DNA dendrimer linked to a targeting moiety and to a siRNA which inhibits expression of HuR in an amount effective to inhibit tumor cell proliferation, inhibit tumor growth and/or treat cancer.
9 . The method according to claim 8 , wherein the siRNA is selected from the group consisting of SEQ ID NO:1/SEQ ID NO:3 and SEQ ID NO:2/SEQ ID NO:4.
10 . The method according to claim 9 , wherein the targeting moiety is selected from the group consisting of folate, transferrin, anti-mesothelin antibody, and combinations thereof.
11 . The method according to claim 8 , wherein the DNA dendrimer is administered in vitro.
12 . The method according to claim 8 , wherein the DNA dendrimer is administered in vivo.
13 . The method according to claim 8 , wherein the DNA dendrimer is administered to a patient with ovarian cancer.
14 . The method according to claim 8 , wherein the DNA dendrimer is administered by injection or infusion.
15 .- 18 . (canceled)
19 . The method according to claim 8 , wherein the targeting moiety is folate and the siRNA is SEQ ID NO:2/SEQ ID NO:4.