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 grand 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 18-19 nucleotides,
wherein the first stretch and the second stretch each comprises a plurality of groups of one or more 2′-O-methyl ribonucleotides, wherein within each stretch each group of the 2′-O-methyl ribonucleotide is flanked on one or both ends by a flanking group of one or more unmodified ribonucleotides,
wherein each 2′-O-methyl ribonucleotide on the first stretch corresponds to an unmodified ribonucleotide on the second stretch, and
wherein each 2′-O-methyl ribonucleotide on the second stretch corresponds to an unmodified ribonucleotide on the first stretch.
2. The double stranded siRNA molecule of claim 1 , wherein the first stretch and the second stretch each has the length of 19 nucleotides.
3. The double stranded siRNA molecule of claim 2 , wherein each of the first strand and the second strand has the length of 21 nucleotides.
4. The double stranded siRNA molecule of claim 1 , wherein the number of 2′-O-methyl ribonucleotides on the first stretch is the same or less than the number of 2′-O-methyl ribonucleotides on the second stretch.
5. The double stranded siRNA molecule of claim 1 , wherein the 5′ ends of the first stretch and the second stretch are unmodified ribonucleotides.
6. The double stranded siRNA molecule of claim 1 , wherein the first stretch comprises single 2′-O-methyl ribonucleotide flanked on one or both sides by unmodified ribonucleotides.
7. The double stranded siRNA molecule of claim 1 , wherein the second stretch comprises groups of one to ten 2′-O-methyl ribonucleotides flanked on one or both sides by unmodified ribonucleotides.
8. The double stranded siRNA molecule of claim 2 , wherein the number of 2′-O-methyl ribonucleotides on the first stretch is the same or less than the number of 2′-O-methyl ribonucleotides on the second stretch.
9. The double stranded siRNA molecule of claim 2 , wherein the 5′ ends of the first stretch and the second stretch is an unmodified ribonucleotide.
10. The double stranded siRNA molecule of claim 2 , wherein the first stretch comprises single 2′-O-methyl ribonucleotide flanked on one or both sides by unmodified ribonucleotides.
11. The double stranded siRNA molecule of claim 2 , wherein the second stretch comprises groups of one to ten 2′-O-methyl ribonucleotides flanked on one or both sides by unmodified ribonucleotides.
12. The double stranded siRNA molecule of claim 3 , wherein the number of 2′-O-methyl ribonucleotides on the first stretch is the same or less than the number of 2′-O-methyl ribonucleotides on the second stretch.
13. The double stranded siRNA molecule of claim 3 , wherein the 5′ ends of the first stretch and the second stretch is an unmodified ribonucleotides.
14. The double stranded siRNA molecule of claim 3 , wherein the first stretch comprises single 2′-O-methyl ribonucleotide flanked on one or both sides by unmodified ribonucleotides.
15. The double stranded siRNA molecule of claim 3 , wherein the second stretch comprises groups of one to ten 2′-O-methyl ribonucleotides flanked on one or both sides by unmodified ribonucleotides.
16. The double stranded siRNA molecule of claim 12 , wherein the 5′ ends of the first stretch and the second stretch is an unmodified ribonucleotides.
17. The double stranded siRNA molecule of claim 12 , wherein the first stretch comprises single 2′-O-methyl ribonucleotide flanked on one or both sides by unmodified ribonucleotides.
18. The double stranded siRNA molecule of claim 12 , wherein the second stretch comprises groups of one to ten 2′-O-methyl ribonucleotides flanked on one or both sides by unmodified ribonucleotides.
19. The double stranded siRNA molecule of claim 16 , wherein the first stretch comprises single 2′-O-methyl ribonucleotide flanked on one or both sides by unmodified ribonucleotides.
20. The double stranded siRNA molecule of claim 16 , wherein the second stretch comprises groups of one to ten 2′-O-methyl ribonucleotides flanked on one or both sides by unmodified ribonucleotides.
21. The double stranded siRNA molecule of claim 19 , wherein the second stretch comprises groups of one to ten 2′-O-methyl ribonucleotides flanked on one or both sides by unmodified ribonucleotides.
22. 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.
23. A composition comprising the double stranded siRNA molecule of claim 1 .
24. The composition of claim 23 , wherein the composition is a pharmaceutical composition.