Modified L-Nucleic Acid

Abstract

A modified L-nucleic acid, containing an L-nucleic acid part conjugated to a non-L-nucleic acid part is described. The conjugate has extended retention time in and demonstrates a delayed elimination from an organism.

1 .- 21 . (canceled) 
     
     
         22 . A modified L-nucleic acid, comprising an L-nucleic acid that binds a target molecule and that is conjugated with a polyethylene glycol (PEG), wherein said modified L-nucleic acid has a biological half life greater than that of said L-nucleic acid, and binds said target molecule. 
     
     
         23 . The modified L-nucleic acid of  claim 22 , wherein said PEG has a molecular weight of more than about 300 Da. 
     
     
         24 . The modified L-nucleic acid of  claim 22 , wherein said L-nucleic acid has a molecular weight of about 300 to 50,000 Da. 
     
     
         25 . The modified L-nucleic acid of  claim 22 , wherein said modified L-nucleic acid has a molecular weight of about 600 to 500,000 Da. 
     
     
         26 . The modified L-nucleic acid of  claim 22 , wherein said modified L-nucleic acid has a molecular weight of more than about 20,000 Da. 
     
     
         27 . The modified L-nucleic acid of  claim 22 , wherein said modified L-nucleic acid has a molecular weight of more than 40,000 Da. 
     
     
         28 . The modified L-nucleic acid of  claim 22 , wherein said PEG is conjugated with a functional group of said L-nucleic acid selected from the group consisting of terminal and non-terminal phosphates, terminal and non-terminal sugar portions, natural and non-natural purine bases, and natural and non-natural pyrimidine bases. 
     
     
         29 . The modified L-nucleic acid of  claim 22 , wherein said PEG is conjugated with a 2′-OH—, a 3′-OH—, a 5′-OH—, or a derivative of each, or a sugar of said L-nucleic acid. 
     
     
         30 . The modified L-nucleic acid of  claim 22 , wherein said PEG is conjugated at the 5 or 6 position of a pyrimidine base. 
     
     
         31 . The modified L-nucleic acid of  claim 22 , wherein said PEG is conjugated at a purine base. 
     
     
         32 . The modified L-nucleic acid of  claim 22 , wherein said PEG is conjugated to an exocyclic amine group, endocyclic amine group or keto group of a purine or pyrimidine base. 
     
     
         33 . The modified L-nucleic acid of  claim 22 , wherein said PEG is linear or branched. 
     
     
         34 . The modified L-nucleic acid of  claim 22 , comprising a linker between said L-nucleic acid and said PEG. 
     
     
         35 . The modified L-nucleic acid of  claim 34 , wherein said linker comprises a 6-aminohexylphosphate at the 5′-OH end of said L-nucleic acid. 
     
     
         36 . The modified L-nucleic acid of  claim 35 , wherein said PEG is coupled to the free amine of said 6-aminohexylphosphate. 
     
     
         37 . The modified L-nucleic acid of  claim 22 , wherein said PEG is conjugated at the 8 position of a purine. 
     
     
         38 . A composition comprising the modified L-nucleic acid of  claim 22  and a pharmaceutically acceptable carrier, excipient or diluent.