Treatment of angiogenesis-associated diseases using rna complexes that target angpt2 and pdgfb

Abstract

In certain aspects, provided herein are RNA complexes (e.g., asymmetric RNA complexes, such as asiRNAs or cell penetrating asiRNAs) that inhibit ANGPT2 and/or PDGFB expression and are therefore useful for treating angiogenesis-associated diseases, such as cancer, AMD, and DME.

1 . An RNA complex comprising an antisense strand of at least 19 nucleotides (nt) in length having sequence complementarity to an ANGPT2 mRNA sequence or a PDGFB mRNA sequence and a sense strand of 15 to 17 nt in length having sequence complementarity to the antisense strand, wherein the antisense strand and the sense strand form a complex in which the 5′ end of the antisense strand and the 3′ end of the sense strand form a blunt end. 
     
     
         2 . (canceled) 
     
     
         3 . The RNA complex of  claim 1 , wherein the antisense strand is 19 to 21 nt in length. 
     
     
         4 .- 6 . (canceled) 
     
     
         7 . The RNA complex of  claim 1 , wherein the antisense strand is at least 24 nt in length. 
     
     
         8 .- 10 . (canceled) 
     
     
         11 . The RNA complex of  claim 1 , wherein the sense strand has a sequence selected from the sense strand sequences listed in Table 1, Table 2, Table 3, Table 4, Table 5, and Table 6. 
     
     
         12 . The RNA complex of  claim 1 , wherein the antisense strand has a sequence selected from the antisense strand sequences listed in Table 1, Table 2, Table 3, Table 4, Table 5, and Table 6. 
     
     
         13 .- 16 . (canceled) 
     
     
         17 . The RNA complex of  claim 1 , wherein the RNA complex comprises a chemical modification. 
     
     
         18 . The RNA complex of  claim 17 , wherein the chemical modification is a 2′-O-methylated nucleoside, a phosphorothioate bond or a hydrophobic moiety. 
     
     
         19 . (canceled) 
     
     
         20 . The RNA complex of  claim 18 , wherein the hydrophobic moiety is a cholesterol moiety. 
     
     
         21 .- 28 . (canceled) 
     
     
         29 . The RNA complex of  claim 18 , wherein the RNA complex comprises at least one phosphorothioate bond. 
     
     
         30 .- 37 . (canceled) 
     
     
         38 . The RNA complex of  claim 17 , wherein the RNA complex is a modified RNA complex listed in Table 2, Table 3, Table 5, and Table 6. 
     
     
         39 . The RNA complex of  claim 1 , wherein the RNA complex is capable of penetrating the cellular membrane of a cell in the absence of a delivery vehicle. 
     
     
         40 .- 46 . (canceled) 
     
     
         47 . A method of inhibiting an angiogenesis-associated disease in a subject comprising administering the RNA complex of  claim 1 . 
     
     
         48 .- 49 . (canceled) 
     
     
         50 . The method of  claim 47 , wherein the angiogenesis-associated disease is AMD. 
     
     
         51 . The method of  claim 50 , wherein the AMD is wet AMD. 
     
     
         52 . The method of  claim 50 , wherein the AMD is dry AMD. 
     
     
         53 .- 70 . (canceled) 
     
     
         71 . A pharmaceutical composition comprising an RNA complex of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         72 . A method of inhibiting angiogenesis in a subject, comprising administering to the subject a pharmaceutical composition of  claim 71 . 
     
     
         73 . (canceled) 
     
     
         74 . The method of  claim 72 , comprising administering the pharmaceutical composition to a tumor or to the eye in the subject. 
     
     
         75 .- 92 . (canceled) 
     
     
         93 . The method  claim 50 , further comprising administering a second agent for the treatment of AMD. 
     
     
         94 . (canceled) 
     
     
         95 . The method of  claim 93 , wherein the second agent is ranibizumab, bevacizumab, pegaptanib, or afibercept.