Nuclease-resistant dna analogues

Abstract

The present invention provides stable, nuclease-resistant TNA, TNA-DNA and TNA-RNA oligonucleotides, wherein the oligonucleotides are completely resistant to enzymatic degradation for at least 24-72 hours. Methods of synthesis and use in diagnostic and therapeutic applications are also provided.

What is claimed is: 
     
         1 . A stable, nuclease-resistant TNA-RNA oligonucleotide, wherein the TNA-RNA oligonucleotide comprises an effective amount of TNA to provide resistance to enzymatic degradation in a biological environment wherein at least half the oligonucleotides are TNA. 
     
     
         2 . The nuclease-resistant TNA-RNA oligonucleotide of  claim 1 , wherein the TNA-RNA oligonucleotide is resistant to enzymatic degradation by snake venom phosphodiesterase, RNAse A, RQ1 DNAse, and Turbo DNAse for at least 72 hours. 
     
     
         3 . The nuclease-resistant TNA-RNA oligonucleotide of  claim 1 , wherein the effective amount of TNA comprises at least two TNA nucleic acids. 
     
     
         4 . The nuclease-resistant TNA-RNA oligonucleotide of  claim 1 , wherein the effective amount of TNA comprises at least three TNA nucleic acids. 
     
     
         5 . The nuclease-resistant TNA-RNA oligonucleotide of  claim 1 , wherein the TNA residues alternate with RNA residues. 
     
     
         10 . The nuclease-resistant TNA-RNA oligonucleotide of  claim 1 , wherein the TNA-RNA oligonucleotide forms a duplex wherein a portion of the oligonucleotide comprises TNA that is able to anneal to a complementary portion of the oligonucleotide containing RNA, wherein the duplex is resistant to enzymatic degradation in a biological environment of the TNA-RNA duplex. 
     
     
         11 . The nuclease-resistant TNA-RNA oligonucleotide of  claim 10 , wherein the TNA-RNA duplex is resistant to enzymatic degradation by snake venom phosphodiesterase, RNAse A, RQ1 DNAse, and Turbo DNAse for at least 24 hours. 
     
     
         12 . The nuclease-resistant TNA-RNA oligonucleotide of  claim 10 , wherein the TNA-RNA duplex is resistant to enzymatic degradation for at least 72 hours. 
     
     
         13 . A TNA-RNA duplex comprising a RNA strand and a complementary TNA strand, wherein the duplex comprises an effective amount of TNA to provide resistance to enzymatic degradation in a biological environment and wherein the TNA strand is able to anneal to the RNA strand. 
     
     
         14 . The TNA-RNA duplex of  claim 13 , wherein the duplex is resistant to enzymatic degradation for at least 24 hours. 
     
     
         15 . The TNA-RNA duplex of  claim 14 , wherein the duplex is resistant to enzymatic degradation for at least 72 hours. 
     
     
         16 . A method of preparing a nuclease-resistant TNA-RNA oligonucleotide of  claim 1 , the method comprising inserting an effective amount of TNA into a sample of RNA to yield a TNA-RNA oligonucleotide, wherein the TNA-RNA oligonucleotide is resistant to enzymatic degradation in a biological environment. 
     
     
         17 . The method of  claim 16 , wherein the TNA-RNA oligonucleotide is resistant to enzyme degradation for at least 24 hours. 
     
     
         18 . The method of  claim 16 , wherein the TNA residues alternate with RNA residues. 
     
     
         19 . The method of  claim 16 , wherein the TNA-RNA oligonucleotide is resistant to enzyme degradation for at least 72 hours. 
     
     
         20 . The method of  claim 16 , wherein the TNA-RNA oligonucleotide comprises a portion of RNA continuous with a portion of the oligonucleotide comprising TNA that is able to anneal to a complementary portion of the oligonucleotide containing RNA.