2'-modified oligonucleotides

Abstract

Compositions and methods are provided for the treatment and diagnosis of diseases amenable to modulation of the production of selected proteins. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the 2′-deoxyfuranosyl moieties of the nucleoside unit is modified. Treatment of diseases caused by various viruses and other causative agents is provided.

1 . A pharmaceutical composition comprising an oligonucleotide having a plurality of covalently-bound nucleosides that individually include a ribose or deoxyribose sugar portion and a base portion, wherein: 
 said nucleosides are joined together by internucleoside linkages such that the base portion of said nucleosides form a mixed base sequence;    at least one of said nucleosides include a modified ribofuranosyl moiety bearing a 2′-fluoro substituent;    provided that at least two of said nucleosides are 2′-fluoro modified ribofuranosyl nucleosides when said internucleoside linkages are phosphodiester linkages; and    a pharmaceutical carrier.    
     
     
         2 . A pharmaceutical composition of  claim 1  having 8 to 40 nucleoside linked nucleosides.  
     
     
         3 . A pharmaceutical composition comprising an oligonucleotide having 8 to 40 covalently-bound nucleosides that individually include a ribose or deoxyribose sugar portion and a base portion, wherein: 
 said nucleosides are joined together by internucleoside linkages such that the base portion of said nucleosides form a mixed base sequence;    at least one of said nucleosides include a modified ribofuranosyl moiety bearing a 2′-fluoro substituent;    provided that at least two of said nucleosides are 2′-fluoro modified ribofuranosyl nucleosides when said internucleoside linkages are phosphodiester linkages; and    a pharmaceutical carrier.    
     
     
         4 . A pharmaceutical composition comprising an oligonucleotide having at least 12 covalently-bound nucleosides that individually include a ribose or deoxyribose sugar portion and a base portion, wherein: 
 said nucleosides are joined together by internucleoside linkages such that the base portion of said nucleosides form a mixed base sequence;    at least one of said nucleosides includes a modified ribofuranosyl moiety bearing a 2′-fluoro substituent; and    a pharmaceutical carrier.    
     
     
         5 . A pharmaceutical composition comprising an oligonucleotide having at least 12 covalently-bound nucleosides that individually include a ribose or deoxyribose sugar portion and a base portion, wherein: 
 said nucleosides are joined together by internucleoside linkages such that the base portion of said nucleosides form a mixed base sequence;    at least one of said nucleosides includes a modified ribofuranosyl moiety bearing a 2′-fluoro substituent; and    a pharmaceutical carrier for one of ophthalmic, vaginal, rectal, intranasal, or transdermal administration.