Method and medicament for inhibiting the expression of a given gene
The invention relates to an oligoribonucleotide of double-stranded structure (dsRNA) for inhibiting the expression of a given target gene in mammalian cells and a method of mediating RNA interference of an mRNA of a gene in mammalian cells using the dsRNA.
1 . An oligoribonucleotide of double-stranded structure (dsRNA) for inhibiting the expression of a given target gene in mammalian cells, wherein the dsRNA has 15 to 49 base pairs and has a complementary region I that is incorporated in the dsRNA, and wherein the complementary region I has not more than 49 nucleotide pairs.
2 . The dsRNA of claim 1 , wherein at least one of said strands comprises at least one chemically modified nucleotide.
3 . The dsRNA of claim 2 , wherein said chemically modified nucleotide is a 2′-modified nucleotide.
4 . The dsRNA of claim 3 , wherein said 2′-modified nucleotide is a 2′-methyl substituted nucleotide.
5 . The dsRNA of claim 3 , wherein said 2′-modified nucleotide is a 2′-amino substituted nucleotide.
6 . The dsRNA of claim 3 , wherein said chemically modified nucleotide is a locked nucleotide.
7 . The dsRNA of claim 1 , wherein the target gene is a mammalian gene or a viral gene.
8 . The dsRNA of claim 1 , wherein the target gene is selected from the group consisting of an oncogene, a cytokine gene, an Id protein gene, a developmental gene, a PKR gene and a prion gene.
9 . The dsRNA of claim 1 , wherein inhibiting the expression of said target gene further comprises inhibiting expression at a concentration of the dsRNA that is lower by one order of magnitude than a concentration required for a corresponding single-stranded oligoribonucleotide to inhibit expression.
10 . The dsRNA of claim 1 , wherein the dsRNA is enclosed by a micellar structure.
11 . The dsRNA of claim 10 , wherein the micellar structure comprises a liposome.
12 . The dsRNA of claim 1 , wherein the target gene is expressed in eukaryotic cells.
13 . The dsRNA of claim 1 , wherein the ends of the dsRNA are modified in order for the double-stranded structure to counteract degradation.
14 . The dsRNA of claim 1 , wherein at least two dsRNAs which differ from each other are introduced into the cell.