Patent ID: 8790919

Claim:
A method of modulating the expression of a target RNA molecule in a eukaryotic cell comprising the step of contacting the cell with an oligonucleotide consisting of 8 to 80 linked nucleosides and having a) a first region of nucleotides, each having a first conformation which, when the oligonucleotide is bound to the target RNA molecule, forms a substrate for cleavage by an RNase; b) a second region of nucleotides, each having a second conformation which, when the oligonucleotide is bound to the target RNA molecule does not form a substrate for cleavage by an RNase, and c) a transition moiety positioned between the first and the second regions which modulates the transmission of the conformation of the second region into the first region, wherein the transition moiety comprises at least one modified nucleotide that does not form hydrogen bonds with the target RNA molecule, wherein the modified nucleotide is (i) a modified or unmodified sugar abasic nucleotide, or (ii) comprises a modified nucleobase selected from the group consisting of a universal base, a hydrophobic base, and a fluorinated nucleobase.