2'-deoxy-2'-fluoro modified RNA

Abstract

The present invention refers to an RNA molecule with catalytic activity comprising at least one modified nucleoside, wherein the hydroxy group at the 2′-position of the ribose sugar is replaced by a modifier group, selected from halo, sulfhydryl, azido, amino, monosubstituted amino and disubstituted amino groups, a process for the preparation of modified RNA molecules and the use of modified RNA molecules as therapeutic agents and biocatalysts.

1 . An RNA molecule of length between about 12 and about 36 nucleotides comprising at least one modified nucleotide, wherein the modified nucleotide is a 2′-deoxy-2′-fluoro nucleotide.  
     
     
         2 . The RNA molecule of  claim 1 , wherein all pyrimidine nucleotides present in said RNA are 2′-deoxy-2′-fluoro pyrimidine nucleotides.  
     
     
         3 . The RNA molecule of  claim 1 , wherein the modified nucleotides in said RNA include at least one 2′-deoxy-2′-fluoro cytidine or 2′-deoxy-2′-fluoro uridine nucleotide.  
     
     
         4 . The RNA molecule of  claim 1 , wherein the modified nucleotides in said RNA include at least one 2′-fluoro cytidine and at least one 2′-deoxy-2′-fluoro uridine nucleotides.  
     
     
         5 . The RNA molecule of  claim 1 , wherein all uridine nucleotides present in said RNA are 2′-deoxy-2′-fluoro uridine nucleotides.  
     
     
         6 . The RNA molecule of  claim 1 , wherein all cytidine nucleotides present in said RNA are 2′-deoxy-2′-fluoro cytidine nucleotides.  
     
     
         7 . The RNA molecule of  claim 1 , wherein all adenosine nucleotides present in said RNA are 2′-deoxy-2′-fluoro adenosine nucleotides.  
     
     
         8 . The RNA molecule of  claim 1 , wherein all guanosine nucleotides present in said RNA are 2′-deoxy-2′-fluoro guanosine nucleotides.  
     
     
         9 . The RNA of  claim 1 , further comprising at least one modified internucleotidic linkage.  
     
     
         10 . The RNA of  claim 9 , wherein said internucleotidic linkage is a phosphorothioate linkage.  
     
     
         11 . The RNA molecule of  claim 1 , wherein one or more said 2′-deoxy-2′-fluoronucleotides are present at specifically selected locations in said RNA that are sensitive to cleavage by ribonucleases.  
     
     
         12 . The RNA of  claim 11 , wherein said specifically selected locations that are sensitive to cleavage by ribonucleases comprise pyrimidine nucleotides.  
     
     
         13 . The RNA molecule of  claim 1 , wherein said RNA is associated with one or more cellular proteins.  
     
     
         14 . A method of increasing the stability of an RNA molecule against cleavage by ribonucleases, comprising introducing at least one modified nucleotide into said RNA, wherein said modified nucleotide is a 2′-deoxy-2′-fluoro nucleotide.  
     
     
         15 . The method of  claim 14 , wherein all pyrimidine nucleotides present in said RNA are replaced by 2′-deoxy-2′-fluoro pyrimidine nucleotides.  
     
     
         16 . The method of  claim 14 , wherein at least one of the pyrimidine nucleotide in said RNA is replaced with a 2′-deoxy-2′-fluoro nucleotide.  
     
     
         17 . The method of  claim 14 , wherein all pyrimidine nucleotides present in said RNA are replaced with 2′-deoxy-2′-fluoro pyrimidine nucleotides.  
     
     
         18 . The method of  claim 14 , wherein at least one of the cytidine nucleotides in said RNA is replaced with a 2′-fluoro cytidine nucleotide.  
     
     
         19 . The method of  claim 14 , wherein at least one of the uridine nucleotides in said RNA is replaced with a 2′-fluoro uridine nucleotide.  
     
     
         20 . The method of  claim 14 , wherein all uridine nucleotides present in said RNA are replaced with 2′-deoxy-2′-fluoro uridine nucleotides.  
     
     
         21 . The method of  claim 14 , wherein all cytidine nucleotides present in said RNA are replaced with 2′-deoxy-2′-fluoro cytidine nucleotides.  
     
     
         22 . The method of  claim 14 , wherein all adenosine nucleotides present in said RNA are replaced with 2′-deoxy-2′-fluoro adenosine nucleotides.  
     
     
         23 . The method of  claim 14 , wherein all guanosine nucleotides present in said RNA are replaced with 2′-deoxy-2′-fluoro guanosine nucleotides.  
     
     
         24 . The RNA of  claim 1  comprising nucleotide sequence that is complementary to nucleotide sequence in a separate RNA.  
     
     
         25 . The RNA of  claim 24 , wherein said separate RNA is a viral RNA.  
     
     
         26 . The RNA of  claim 25 , wherein said viral RNA is HIV RNA.