Oligonucleotides capable of modifying or inhibiting in vivo or in vitro expression of a target gene wherein the oligonucleotide has an antisense sequence, at least one secondary structure, and optionally a supplementary nucleotide sequence located at one and/or both ends of the antisense sequence and wherein the secondary structure disintegrates upon attachment of the oligonucleotide to a target nucleic acid; a pharmaceutical composition containing such an oligonucleotide as an active ingredient; and a method of treatment using such an oligonucleotide.