Double-stranded oligonucleotides (I) consisting of two complementary strands (Ia Ib), each having at one of their 3 and 5 ends 1-5 unpaired nucleotides, forming single-stranded overhangs, are new. One of (Ia) and (Ib) is complementary to a target sequence, of DNA or RNA, that is to be specifically repressed. ACTIVITY : Cytostatic Virucide Anti-HIV Neuroprotective Ophthalmological Antidiabetic Antipsoriatic Antirheumatic Antiarthritic. The oligonucleotide hybrid (A) prepared from sequences of formulae ggggaggcagccauugagacTT gucucaauggcugccuccccTT (lower case indicates ribonucleotides and upper case deoxyribonucleotides) was designed to target the junction of the PML/RARalpha fusion gene associated with promyelocytic leukemia. It (500 ng) was introduced into NIH 3T3 cells, co-transfected with a vector (100 ng) that expressed the PML/RARalpha fusion. Western blotting analysis after 48 hours showed greatly reduced expression of the fusion protein, relative to a control without (A). MECHANISM OF ACTION : Antisense inhibition of gene expression.Linvention a pour objet un oligonucléotide double brin caractérisé en ce quil est constitué de deux séquences oligonucléotidiques complémentaires formant un hybride comprenant chacune à lune de leurs extrémités 3 ou 5 un à cinq nucléotides non appariés formant des bouts simples brins débordant de lhybride, lune desdites séquences oligonucléotidiques étant substantiellement complémentaire dune séquence cible appartenant à une molécule dADN ou dARN à réprimer spécifiquement. Linvention se rapporte aussi à lutilisation desdits oligonucléotides dans des compositions pharmaceutiques notamment pour le traitement des cancers.
