Interfering RNA molecules
The present invention is related to a ribonucleic acid comprising a double stranded structure whereby the double-stranded structure comprises a first strand and a second strand, whereby the first strand comprises a first stretch of contiguous nucleotides and whereby said first stretch is at least partially complementary to a target nucleic acid, and the second strand comprises a second stretch of contiguous nucleotides whereby said second stretch is at least partially identical to a target nucleic acid, and whereby the double stranded structure is blunt ended.
1. A double stranded siRNA molecule against a target nucleic acid, wherein the double stranded siRNA molecule comprises a first strand and a second strand, wherein the first strand comprises a first stretch that is complementary to the target nucleic acid, wherein the second strand comprises a second stretch that has the same length as the first stretch and is complementary to the first stretch, wherein the first strand and the second strand form a double-stranded structure comprising the first stretch and the second stretch,
wherein the first stretch and the second stretch each has the length of 17-21 nucleotides, wherein the first stretch and the second stretch each comprises a plurality of groups of 2′-O-methyl ribonucleotides flanked on one or both sides by a flanking group of unmodified ribonucleotides or modified ribonucleotides different from 2′-O-methyl ribonucleotides, and
wherein at least one of the two strands has an overhang of at least one nucleotide at the 3′-end.
2. The double stranded siRNA molecule of claim 1 , wherein the number of 2′-O′methyl ribonucleotides in each of the plurality of groups of 2′-O-methyl ribonucleotides is one to ten.
3. The double stranded siRNA molecule of claim 1 , wherein the number of unmodified ribonucleotides or modified ribonucleotides different from 2′-O-methyl ribonucleotides in each of the flanking groups is one to ten.
4. The double stranded siRNA molecule of claim 1 , wherein the first stretch and the second stretch each has the length of 18-19 nucleotides.
5. The double stranded siRNA molecule of claim 1 , wherein the plurality of groups of 2′-O-methyl ribonucleotides are flanked on one or both sides by a flanking group of modified ribonucleotides different from 2′-O-methyl ribonucleotides.
6. The double stranded siRNA molecule of claim 5 , wherein the modified ribonucleotides different from 2′-O-methyl ribonucleotides are 2′-fluoro ribonucleotides.
7. The double stranded siRNA molecule of claim 6 , wherein each 2′-fluoro ribonucleotide on the first stretch corresponds to a 2′-O-methyl ribonucleotide on the second stretch.
8. The double stranded siRNA molecule of claim 6 , wherein each 2′-fluoro ribonucleotide on the second stretch corresponds to a 2′-O-methyl ribonucleotide on the first stretch.
9. The double stranded siRNA molecule of claim 1 , wherein the plurality of groups of 2′-O-methyl ribonucleotides are flanked on one or both sides by a flanking group of unmodified ribonucleotides.
10. The double stranded siRNA molecule of claim 9 , wherein each 2′-O-methyl ribonucleotide on the first stretch corresponds to an unmodified ribonucleotide on the second stretch.
11. The double stranded siRNA molecule of claim 9 , wherein each 2′-O-methyl ribonucleotide on the second stretch corresponds to an unmodified ribonucleotide on the first stretch.
12. The double stranded siRNA molecule of claim 9 , wherein the first stretch comprises single 2′-O-methyl ribonucleotides flanked on one or both sides by unmodified ribonucleotides.
13. The double stranded siRNA molecule of claim 9 , wherein the second stretch comprises groups of one to ten 2′-O-methyl ribonucleotides flanked on one or both sides by unmodified ribonucleotides.
14. The double stranded siRNA molecule of claim 1 , wherein the 3′-end of the first strand has an overhang.
15. The double stranded siRNA molecule of claim 14 , wherein the overhang has one to eight nucleotides.
16. The double stranded siRNA molecule of claim 1 , wherein the 3′-end of the second strand has an overhang.
17. The double stranded siRNA molecule of claim 16 , wherein the overhang has one to eight nucleotides.
18. The double stranded siRNA molecule of claim 1 , wherein one end of the double stranded siRNA molecule is blunt ended.
19. The double stranded siRNA molecule of claim 1 , wherein the blunt end is at the 5′-end of the first strand and 3′-end of the second strand.
20. The double stranded siRNA molecule of claim 1 , wherein the first stretch and the second stretch each has the length of 21 nucleotides.
21. The double stranded siRNA molecule of claim 1 , wherein the target nucleic acid is selected from the group comprising structural genes, housekeeping genes, transcription factors, motility factors, cell cycle factors, cell cycle inhibitors, enzymes, growth factors, cytokines, and tumor suppressors.
22. A composition comprising the double stranded siRNA molecule of claim 1 .
23. The composition of claim 11 , wherein the composition is a pharmaceutical composition.