Organic compositions to treat hsf1-related diseases

Abstract

The present disclosure relates to methods of treating heat shock factor 1 (HSF1)-related diseases such as cancer autoimmune and viral diseases, using a therapeutically effective amount of a RNAi agent to HSF.

We claim: 
     
         1 . A composition comprising a RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent specific to HSF1 provided in Table A1. 
     
     
         2 . The composition of  claim 1 , wherein the composition further comprises a second RNAi agent to HSF1. 
     
     
         3 . The composition of  claim 1 , wherein the RNAi agent comprises at least one modified backbone and/or at least one 2′-modified nucleotide. 
     
     
         4 . The composition of  claim 1 , wherein the RNAi agent is ligated to one or more agent selected from: one or more diagnostic compound, reporter group, cross-linking agent, nuclease-resistance conferring moiety, natural or unusual nucleobase, lipophilic molecule, cholesterol, lipid, lectin, steroid, uvaol, hecigenin, diosgenin, terpene, triterpene, sarsasapogenin, Friedelin, epifriedelanol-derivatized lithocholic acid, vitamin, carbohydrate, dextran, pullulan, chitin, chitosan, synthetic carbohydrate, oligo lactate 15-mer, natural polymer, low- or medium-molecular weight polymer, inulin, cyclodextrin, hyaluronic acid, protein, protein-binding agent, integrin-targeting molecule, polycationic, peptide, polyamine, peptide mimic, and/or transferrin. 
     
     
         5 . The composition of  claim 1 , wherein the composition is a pharmaceutically effective formulation. 
     
     
         6 . The composition of  claim 2 , wherein the composition is a pharmaceutically effective formulation. 
     
     
         7 . The composition of  claim 1 , wherein all the pyrimidine nucleotides of the RNAi agent are 2′-O-methyl modified nucleotides. 
     
     
         8 . A method of treating a HSF1-related disease in a subject, the method comprising administering to the subject a therapeutically effective amount of a composition comprising a RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent specific to HSF1 provided in Table A1. 
     
     
         9 . The method of  claim 8 , wherein the HSF1-related disease is cancer, or autoimmune, or a viral disease. 
     
     
         10 . The method of  claim 8 , wherein the method further comprises administering an additional treatment for cancer, or autoimmune, or a viral disease. 
     
     
         11 . The method of  claim 10 , wherein the method further comprises administering an additional RNAi agent to HSF1. 
     
     
         12 . The method of  claim 10 , wherein the additional treatment is a HSP90 inhibitor. 
     
     
         13 . The method of  claim 12 , wherein the HSP90 inhibitor is AUY922. 
     
     
         14 . A method of inhibiting the expression of a HSF1 gene in an subject, comprising administering to the subject a therapeutically effective amount of a composition comprising a RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent specific to HSF1 provided in Table A1. 
     
     
         15 . The method of  claim 14 , wherein the HSF1-related disease is cancer, or autoimmune, or a viral disease.