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 . A composition comprising a RNAi agent comprising a first strand and a second strand, wherein the first strand and second strand comprise at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the first and second strand, respectively, of a RNAi agent specific to HSF1 provided in Table A1. 
     
     
         6 . The composition of  claim 1 , wherein the composition comprises a second RNAi agent to HSF1. 
     
     
         7 . The composition of  claim 1 , wherein the RNAi agent comprises a phosphorothioate and/or a 2′-modified nucleotide. 
     
     
         8 . The composition of  claim 1 , wherein the RNAi agent is ligated to one or more agents, the agent selected from a: 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. 
     
     
         9 . A method of treating a HSF1-related disease in an individual, comprising the step of administering to the individual 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. 
     
     
         10 . The method of  claim 9 , wherein the HSF1-related disease is cancer, or autoimmune, or a viral disease. 
     
     
         11 . The method of  claim 9 , wherein the method further comprises the step of administering an additional treatment for cancer, or autoimmune, or a viral disease. 
     
     
         12 . The method of  claim 11 , wherein the method further comprises the step of administering an additional RNAi agent to HSF1. 
     
     
         13 . A method of inhibiting the expression of the HSF1 gene in an individual, comprising the step of administering to the individual 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. 
     
     
         14 . The method of  claim 13 , wherein the HSF1-related disease is cancer, or autoimmune, or a viral disease. 
     
     
         15 . A medicament for use in an RNAi formulation 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. 
     
     
         16 . Any composition above in a pharmaceutically effective formulation. 
     
     
         17 . The composition according to  claim 1 , for use in a method of treating a HSF1-related disease in an individual, the method comprising the step of administering to the individual a therapeutically effective amount of a composition according to  claim 1 . 
     
     
         18 . The use of a composition according to  claim 1 , in the manufacture of a medicament for the treatment of a HSF1-related disease. 
     
     
         19 . The composition of  claim 1 , wherein all the pyrimidines are 2′ O-methyl-modified nucleotides. 
     
     
         20 . The composition of  claim 5 , wherein all the pyrimidines are 2′ O-methyl-modified nucleotides. 
     
     
         21 . The method of  claim 11 , wherein the additional treatment is a HSP90 inhibitor. 
     
     
         22 . The method of  claim 21 , wherein the HSP90 inhibitor is AUY922.