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 nucleotide monomer(s). By a hydroxymethyl substituted
nucleotide monomer is understood a nucleotide monomer containing a
hydroxymethyl group (that may be unsubstituted, O-substituted for example
with a conjugating group, or converted into an optionally substituted or
conjugated aminomethyl group). This hydroxymethyl group is not partaking
in formation of an internucleotide linkage and is not the hydroxymethyl
group (containing the 5'-hydroxy group) of a natural RNA monomer. The RNA
complexes of the invention may be useful for therapeutic applications,
diagnostic applications or research applications. The complexes include
short interfering RNA complexes (siRNA duplexes) comprising an antisense
strand and a continued or a discontinued passenger strand ("sense
strand") capable of regulating gene expression. At least one of these
strands, 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 strands") that are modified with at
least one, but optionally more that one, hydroxymethyl substituted
nucleotide monomer(s). Such single stranded RNA strands are to be
considered included whenever the term RNA complexes is used in this
patent application. The complexes of the invention display enhanced
stability towards nucleolytic degradation relative to the corresponding
complexes comprised entirely from natural RNA monomers.