| 摘要 |
The present invention is directed to RNA oligonucleotides or complexes of RNA oligonucleotides, denoted herein together as RNA complexes, containing at least one, but optionally more that one, hydroxymethyl substituted nucleo tide monomer(s). By a hydroxymethyl substituted nucleotide monomer is unders tood a nucleotide monomer containing a hydroxymethyl group (that may be unsu bstituted, O-substituted for example with a conjugating group, or converted into an optionally substituted or conjugated aminomethyl group). This hydrox ymethyl group is not partaking in formation of an internucleotide linkage an d is not the hydroxymethyl group (containing the 5'-hydroxy group) of a natu ral RNA monomer. The RNA complexes of the invention may be useful for therap eutic applications, diagnostic applications or research applications. The co mplexes include short interfering RNA complexes (siRNA duplexes) comprising an antisense strand and a continued or a discontinued passenger strand ("sen se strand") capable of regulating gene expression. At least one of these str ands, possible more than one of these strands, are modified with one or more hydroxymethyl substituted nucleotide monomer(s) of this invention, that can be positioned at the 3'-end, at the 5'-end or internally. The RNA complexes of the invention can also be single stranded RNA oligonucleotides ("RNA str ands") that are modified with at least one, but optionally more that one, hy droxymethyl substituted nucleotide monomer(s). Such single stranded RNA stra nds are to be considered included whenever the term RNA complexes is used in this patent application. The complexes of the invention display enhanced st ability towards nucleolytic degradation relative to the corresponding comple xes comprised entirely from natural RNA monomers. |
