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 the same length as said first stretch and 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 first stretch and said second stretch each comprises contiguous alternating ribonucleotides modified with an O-alkyl group, said alternating ribonucleotides modified with an O-alkyl group alternating with unmodified or modified ribonucleotides and wherein the ribonucleotides modified with an O-alkyl group of said first strand are shifted by one ribonucleotide relative to the ribonucleotides modified with an O-alky group of the second strand;
wherein each stretch consists of at least 17 and fewer than 30 ribonucleotides.
2. The nucleic acid molecule according to claim 1 , wherein the double-stranded structure is blunt ended on both ends of the double strand.
3. 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 alternate with unmodified ribonucleotides, 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 and each stretch consists of at least 17 and fewer than 30 ribonucleotides.
4. 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 alternate with modified ribonucleotides, 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 and each stretch consists of at least 17 and fewer than 30 ribonucleotides.
5. The nucleic acid molecule according to claim 4 , 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 alternate with ribonucleotides that have been modified at the 2′-position with an amino, fluoro, methoxy, alkoxy or alkyl group.
6. The nucleic acid molecule according to claim 4 , wherein said double-stranded structure is blunt ended on at least one end.
7. The nucleic acid molecule according to claim 4 , wherein said double-stranded structure has at least one overhang of one to eight nucleotides.
8. The nucleic acid molecule according to claim 7 , wherein said at least one overhang is at the 3′ end of the first strand.
9. The nucleic acid molecule according to claim 7 , wherein said at least one overhang is at the 5′ end of the first strand.
10. The nucleic acid molecule according to claim 7 , wherein said at least one overhang is at the 3′ end of the second strand.
11. The nucleic acid molecule according to claim 7 , wherein said at least one overhang is at the 5′ end of the second strand.
12. The nucleic acid molecule according to claim 3 , wherein the 5′ ribonucleotide of said first stretch is modified with an 2′-O-alkyl group and alternates with an unmodified ribonucleotide.
13. The nucleic acid molecule according to claim 5 , wherein the 5′ ribonucleotide of said first stretch is modified with an O-alkyl group and alternates with an ribonucleotide modified at the 2′ position with an amino group.
14. The nucleic acid molecule according to claim 5 , wherein the 5′ ribonucleotide of said first stretch is modified with an O-alkyl group and alternates with an ribonucleotide modified at the 2′ position with a fluoro group.
15. The nucleic acid molecule according to claim 5 , wherein the 5′ ribonucleotide of said first stretch is modified with an O-alkyl group and alternates with an ribonucleotide modified at the 2′ position with a methoxy group.
16. The nucleic acid molecule according to claim 5 , wherein the 5′ ribonucleotide of said first stretch is modified with an O-alkyl group and alternates with an ribonucleotide modified at the 2′ position with an alkoxy group.
17. The nucleic acid molecule according to claim 5 , wherein the 5′ ribonucleotide of said first stretch is modified with an O-alkyl group and alternates with an ribonucleotide modified at the 2′ position with an alkyl group.
18. The nucleic acid molecule according to claim 12 , wherein said 2′-O-alkyl group is a 2′-O-methyl group.
19. The nucleic acid molecule according to claim 13 , wherein said 2′-O-alkyl group is a 2′-O-methyl group.
20. The nucleic acid molecule according to claim 14 , wherein said 2′-O-alkyl group is a 2′-O-methyl group.
21. The nucleic acid molecule according to claim 15 , wherein said 2′-O-alkyl group is a 2′-O-methyl group.
22. The nucleic acid molecule according to claim 16 , wherein said 2′-O-alkyl group is a 2′-O-methyl group.
23. The nucleic acid molecule according to claim 17 , wherein said 2′-O-alkyl group is a 2′-O-methyl group.