Una oligomer active structures for therapeutic agents

Abstract

This invention provides oligomer structures for therapeutic agents, the oligomers composed of one or more UNA nucleomonomers, along with nucleic acid monomers. The UNA oligomers may be used as therapeutic agents for treating or preventing disease. The UNA oligomers can be capable of modulating or silencing gene expression, through RNA interference or other modalities, and may have an antisense strand and a sense strand.

What is claimed is: 
     
         1 - 23 . (canceled) 
     
     
         24 . An oligomeric compound comprising one or more 2′-3′-seco-monomers and one or more ribonucleic acid monomers, the oligomeric compound comprising a sense strand and an antisense strand that together form one double stranded region of 15 to 24 base pairs, wherein one or both of the last two positions of the 3′-end of the sense strand are occupied by the same or different 2′-3′-seco-monomer, and wherein one or both of the last two positions of the 3′-end of the antisense strand are occupied by the same or different 2′-3′-seco-monomer. 
     
     
         25 . The oligomeric compound of  claim 24 , wherein the double-stranded region has 19 or 20 base pairs. 
     
     
         26 . The oligomeric compound of  claim 24 , wherein the sense strand and the antisense strand are each 21 or 22 nucleomonomers in length. 
     
     
         27 . The oligomeric compound of  claim 24 , wherein the oligomer has a blunt end. 
     
     
         28 . The oligomeric compound of  claim 24 , wherein the antisense strand has a region of at least 15 contiguous nucleomonomers corresponding to any 15 contiguous nucleomonomers of SEQ ID NOs: 12, 34, 56, 78, 100, 124, or 147. 
     
     
         29 . The oligomeric compound of  claim 24 , wherein the antisense strand has a region of at least 15 contiguous nucleomonomers corresponding to any 15 contiguous nucleomonomers of SEQ ID NOs: 169, 185, 201, 217, or 233. 
     
     
         30 . The oligomeric compound of  claim 24 , wherein the acyclic 2′-3′-seco-monomer is selected from the group of monomers D, F, G, H, I, and J: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein R is selected from the group consisting of a hydrogen, an alkyl group, a cholesterol derivative, a fluorophore, a polyamine, a fatty acid, an amino acid, a saccharide and a polypeptide; 
         wherein Base is any purine, pyrimidine, or derivative or analogue thereof. 
       
     
     
         31 . The oligomeric compound of  claim 24 , further comprising a nucleotide analogue selected from the group consisting of 2′-O-alkyl-RNA monomers, 2′-amino-DNA monomers, 2′-fluoro-DNA monomers, PNA monomers, HNA monomers, ANA monomers, FANA monomers, CeNA monomers, ENA monomers, DNA monomers, and INA monomers. 
     
     
         32 . A method for reducing expression of a gene in a cell comprising preparing an oligomeric compound of  claim 24  and treating the cell with the oligomeric compound. 
     
     
         33 . A method for treating a disease in a human, the disease being selected from inflammatory diseases including rheumatoid arthritis, metabolic diseases including hypercholesterolemia, liver disease, encephalitis, bone fracture, heart disease, viral disease including hepatitis and influenza, and cancer, comprising preparing an oligomeric compound according to  claim 24  and administering the compound to the human.