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 compound comprising 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; and   wherein at least five of said nucleosides includes a modified ribofuranosyl moiety bearing a 2′-fluoro substituent.   
     
     
         2 . A compound comprising 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; and   wherein at least two consecutive nucleosides in said mixed base sequence are nucleosides that include a modified ribofuranosyl moiety bearing a 2′-fluoro substituent.   
     
     
         3 . A compound of  claim 2  wherein at least three consecutive nucleosides in said mixed base sequence are nucleosides that include a modified ribofuranosyl moiety bearing a 2′-fluoro substituent. 
     
     
         4 . A compound comprising 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; and   wherein at least one adenosine, thymidine or cytidine nucleoside of said mixed base sequence includes a modified ribofuranosyl moiety bearing a 2′-fluoro substituent.   
     
     
         5 . A compound comprising 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; and   wherein at least two cytidine nucleosides consecutively located in said mixed base sequence include a modified ribofuranosyl moiety bearing a 2′-fluoro substituent.