OLIGONUCLEOTIDES FOR RNA INTERFERENCE AND BIOLOGICAL APPLICATIONS THEREOF

摘要

The invention relates to compositions comprising double-stranded oligonucleotides of identical or different sequences and/or length, said oligonucleotides having sequences 3′N1N2 . . . Ni-1Ni . . . Nj5′ wherein—3′Ni . . . Nj5′ is half of a double-stranded 19-28 mer oligonucleotide of sequence complementary to a target nucleic acid sequence present in a living cell, and—3′N1 . . . Ni-15′ is a 3-50 mer overhang of sequence allowing oligomerisation of said double-stranded oligonucleotide. Compositions of transfection comprising said oligonucleotide compositions and there used for therapeutical application.

主权项

1. A method for in vivo inhibition of gene expression comprising administering to a mammal in need of such treatment a composition for RNA interference comprising oligomerized double-stranded nucleic acids comprising a plurality of identical or different double-stranded nucleic acids and optionally a linker, wherein each of said identical or different double-stranded nucleic acids consists of a first distinct oligonucleotide and a second distinct oligonucleotide, wherein each of said first and second distinct oligonucleotides consists of 19-28 ribonucleotides at the 5′-end and 3-50 dT or dT and dA nucleotides at the 3′end, wherein the 19-28 ribonulceotides at the 5′-end of the first distinct oligonucleotide are base-paired to the 19-28 ribonucleotides at the 5′-end of the second distinct oligonucleotide and wherein 3-50 dT or dT and dA nucleotides at the 3′-end of the first distinct oligonucleotide and at the 3′-end of the second distinct oligonucleotide are unpaired overhanging sticky dT or dT and dA nucleotides, such that the unpaired overhanging sticky dT or dT and dA nucelotides at the 3′-end of the first distinct oligonucleotide of one of the plurality of identical or different double-stranded nucleic acids are complementary to the unpaired overhanging sticky dT or dT and dA nucleotides at the 3′-end of the second distinct oligonucleotide of another of the plurality of identical or different double-stranded nucleic acids or to a linker having unpaired overhanging sticky dT or dT and dA nucleotides, and wherein said complementary unpaired overhanging sticky dT or dT and dA nucleotides of the plurality of identical or different double-stranded nucleic acids or of the linker are hybridized to form said oligomerized double-stranded nucleic acids.