Compositions and Methods for MYC Messenger RNA Inhibitors

Abstract

The present invention provides compositions and methods of making and using novel MYC mRNA antisense inhibitors. In a particular embodiment, the invention features compositions and methods useful for the treatment of a condition (e.g., cancer).

1 .- 18 . (canceled) 
     
     
         19 . A 2′-O,4′-C-aminomethylene bridged nucleic acid (BNA)-deoxyribonucleic acid-2′O,′-C-aminomethylene bridged nucleic acid (BNA) chimeric antisense oligonucleotide for reduction of MYC activity, wherein the BNA-DNA-BNA chimeric antisense oligonucleotide comprises SEQ ID NO:2 and said deoxynucleic acid comprises at least one modified base. 
     
     
         20 . The BNA-DNA-BNA chimeric antisense oligonucleotide of  claim 19 , wherein said modified base is selected from hypoxanthine, a purine other than guanosine or adenine, pyridin-4-one, pyridin-2-one, phenyl, pseudouracil, 2,4,6-trimethoxy benzene, 3-methyl uracil, dihydrouridine, naphthyl, aminophenyl, 5-alkylcytidine, 5-methylcytidine, 5-alkyluridines (e.g., ribothymidine), 5-halouridine, 5-bromouridine, 6-azapyrimidine, 6-alkylpyrimidine, 6-methyluridine, and propyne. 
     
     
         21 . The BNA-DNA-BNA chimeric antisense oligonucleotide of  claim 19 , comprising a modified nucleotide selected from 2′-methoxyethoxy, 2′-fluoro, 2′-thio, 2′-allyl, 2′-O-[2-(methylamino)-2-oxoethyl], 4′-thio, 4′-CH 2 -O-2′-bridge, 4′-(CH 2 ) 2 —O-2′-bridge, 2′-LNA, and 2′-O-(N-methylcarbamate). 
     
     
         22 . The BNA-DNA-BNA chimeric antisense oligonucleotide of  claim 19 , further comprising a conjugated peptide which undergoes endocytosis via the insulin-like growth factor 1 (IGF1) receptor. 
     
     
         23 . The BNA-DNA-BNA chimeric antisense oligonucleotide of  claim 20 , wherein the peptide comprises SEQ ID NO: 3. 
     
     
         24 . A method for reducing protein expression in a cell, the method comprising contacting the cell with a 2′-O,4′-C-aminomethylene bridged nucleic acid (BNA)-deoxyribonucleic acid-2′O,4′-C-aminomethylene bridged nucleic acid (BNA) chimeric acid sequence inhibitor comprising SEQ ID NO: 2, wherein the protein is at least one of PD-L1, PD-L2, CD47, and Jak2. 
     
     
         25 . The method of  claim 22 , wherein the BNA-DNA-BNA chimeric antisense oligonucleotide further comprises a conjugated peptide which undergoes endocytosis via the insulin-like growth factor 1 (IGF1) receptor. 
     
     
         26 . The method of  claim 23 , wherein the peptide comprises SEQ ID NO: 3. 
     
     
         27 . The method of  claim 22 , wherein the protein is PD-L1, PD-L2, CD47, and Jak2. 
     
     
         28 . The method of  claim 22 , wherein the protein is PD-L1. 
     
     
         29 . The method of  claim 22 , wherein the protein is PD-L2. 
     
     
         30 . The method of  claim 22 , wherein the protein is CD47. 
     
     
         31 . The method of  claim 22 , wherein the protein is Jak2. 
     
     
         32 . The method of  claim 22 , wherein the protein is PD-L1 and PD-L2. 
     
     
         33 . The method of  claim 22 , wherein the protein is PD-L1 and CD47. 
     
     
         34 . The method of  claim 22 , wherein the protein is PD-L1 and Jak2. 
     
     
         35 . The method of  claim 22 , wherein the protein is PD-L1, PD-L2, and CD47. 
     
     
         36 . The method of  claim 22 , wherein the protein is PD-L1, PD-L2, and Jak2. 
     
     
         37 . The method of  claim 22 , wherein the protein is PD-L1, CD47, and Jak2. 
     
     
         38 . A kit comprising the BNA-DNA-BNA chimeric antisense oligonucleotide of  claim 19 , and instructional material for use thereof. 
     
     
         39 . A pharmaceutical composition comprising the BNA-DNA-BNA chimeric antisense oligonucleotide of  claim 19  and a pharmaceutically acceptable carrier.