Conjugates and Compositions for Cellular Delivery

Abstract

This invention features conjugates, degradable linkers, compositions, methods of synthesis, and applications thereof, including cholesterol, folate, galactose, galactosamine, N-acetyl galactosamine, PEG, phospholipid, peptide and human serum albumin (HSA) derived conjugates of biologically active compounds, including antibodies, antivirals, chemotherapeutics, peptides, proteins, hormones, nucleosides, nucleotides, non-nucleosides, and nucleic acids including enzymatic nucleic acids, DNAzymes, allozymes, antisense, dsRNA, siNA, siRNA, triplex oligonucleotides, 2,5-A chimeras, decoys and aptamers.

1 . A compound having Formula III: 
       
         
           
           
               
               
           
         
       
       wherein X comprises a short interfering RNA (siRNA) comprising 2′-fluoro pyrimidines and 2′-O-methyl purines, W comprises a linker molecule selected from the group consisting of amide, phosphate, phosphate ester, phosphoramidate, and thiophosphate ester linkage, and n is an integer from about 1 to about 20. 
     
     
         2 . A compound having Formula 114: 
       
         
           
           
               
               
           
         
       
       wherein X comprises a short interfering RNA (siRNA) comprising 2′-fluoro pyrimidines and 2′-O-methyl purines, W comprises a linker molecule, and n is an integer from about 1 to about 20. 
     
     
         3 . The compound of  claim 2 , wherein W comprises a linker molecule selected from the group consisting of amide, phosphate, phosphate ester, phosphoramidate, and thiophosphate ester linkage. 
     
     
         4 . The compound of  claim 1 , wherein said siRNA molecule comprises a sense strand and an antisense strand, and wherein said sense strand is conjugated with a compound comprising Formula 111. 
     
     
         5 . The compound of  claim 2 , wherein said siRNA molecule comprises a sense strand and an antisense strand, and wherein said sense strand is conjugated with a compound comprising Formula 114.