Interfering RNA molecules
View Patent ↗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 nucleic acid molecule comprising a first strand and a second strand,
wherein said first strand comprises a first stretch that is complementary to a target nucleic acid,
wherein said second strand comprises a second stretch that is complementary to said first stretch,
wherein said first strand and said second strand form a double-stranded structure comprising said first stretch and said second stretch,
wherein said nucleic acid molecule is blunt ended on at least one end, and
wherein each stretch consists of at least 15 and fewer than 30 ribonucleotides and wherein said first stretch and said second stretch each comprises contiguous alternating modified ribonucleotides, said alternating modified ribonucleotides alternating with unmodified or differently modified ribonucleotides.
2. The nucleic acid molecule according to claim 1 , wherein said nucleic acid molecule is blunt ended on the end defined by the 5′ end of the first strand and the 3′ end of the second strand.
3. The nucleic acid molecule according to claim 1 , wherein said nucleic acid molecule is blunt ended on the end defined by the 3′ end of the first strand and the 5′ end of the second strand.
4. The nucleic acid molecule according to claim 1 , wherein the nucleic acid molecule is blunt ended on both ends.
5. The nucleic acid molecule according to claim 1 , wherein each strand consists of at least 17 to 30 ribonucleotides.
6. The nucleic acid molecule according to claim 1 , wherein the first stretch and the second stretch are of the same length.
7. The nucleic acid molecule according to claim 1 , wherein the first strand and the second strand are each 17 to 23 nucleotides long.
8. The nucleic acid molecule according to claim 1 , wherein the first strand and the second strand are each 19 nucleotides long.
9. The nucleic acid molecule according to claim 1 , wherein the first strand and the second strand are each 21 nucleotides long.
10. The nucleic acid molecule according to claim 1 , wherein the first strand and the second strand are each 23 nucleotides long.
11. The nucleic acid molecule according to claim 1 , wherein the modified ribonucleotides are selected from the group consisting of 2′-O-alkyl ribonucleotides, 2′- fluoro ribonucleotides and 2′-amino ribonucleotides.
12. The nucleic acid molecule according to claim 11 , wherein the 2′-O-alkyl ribonucleotides are selected from the group consisting of 2′-methoxy ribonucleotides and 2′-ethoxy ribonucleotides.
13. The nucleic acid molecule according to claim 1 , wherein said alternating modified ribonucleotides of said first strand are shifted by at least one ribonucleotide relative to the unmodified or differently modified ribonucleotides of the second strand.
14. The nucleic acid molecule according to claim 1 , wherein said first stretch and said second stretch each comprises contiguous alternating single 2′-O-alkyl modified ribonucleotides, said single 2′-O-alkyl modified ribonucleotides alternating with unmodified ribonucleotides.
15. The nucleic acid molecule according to claim 14 , wherein the 2′-O-alkyl modified ribonucleotides of said first strand are shifted by one ribonucleotide relative to the 2′-O-alkyl modified ribonucleotides of the second strand.
16. The nucleic acid molecule according to claim 14 , wherein the 2′-O-alkyl modified ribonucleotides are 2′-methoxy ribonucleotides.
17. The nucleic acid molecule according to claim 1 , wherein said first stretch and said second stretch each comprises contiguous alternating single 2′-O-alkyl modified ribonucleotides, said single 2′-O-alkyl modified ribonucleotides alternating with differently modified ribonucleotides.
18. The nucleic acid molecule of claim 17 , wherein the 2′-O-alkyl modified ribonucleotides of said first strand are shifted by one ribonucleotide relative to the 2′-O-alkyl modified ribonucleotides of the second strand.
19. The nucleic acid molecule according to claim 17 , wherein the 2′-O-alkyl modified ribonucleotides are 2′-methoxy ribonucleotides.