Antisense design
View Patent ↗A novel class of pharmaceuticals which comprises a Locked Nucleic Acid (LNA) which can be used in antisense therapy. These novel oligonucleotides have improved antisense properties. The novel oligonucleotides are composed of at least one LNA selected from beta-D-thio/amino-LNA or alpha-L-oxy/thio/amino-LNA. The oligonucleotides comprising LNA may also include DNA and/or RNA nucleotides.
1. An oligonucleotide, 6-30 nucleotide units in length, comprising at least one locked nucleotide unit of formula:
wherein X is O; one of the H in (CH 2 )n is replaced with a C 1-6 alkyl substituent; n is 1; and Base is independently selected from the group consisting of cytosine, methyl cytosine, uracil, thymine, adenine and guanine.
2. The oligonucleotide according to claim 1 , wherein one of the H in (CH 2 )n is replaced with methyl.
3. The oligonucleotide according to claim 1 , wherein Base is cytosine or methyl cytosine.
4. The oligonucleotide according to claim 1 , wherein Base is uracil.
5. The oligonucleotide according to claim 1 , wherein Base is thymine.
6. The oligonucleotide according to claim 1 , wherein Base is adenine.
7. The oligonucleotide according to claim 1 , wherein Base is guanine.
8. The oligonucleotide according to claim 2 , wherein Base is cytosine or methyl cytosine.
9. The oligonucleotide according to claim 2 , wherein Base is uracil.
10. The oligonucleotide according to claim 2 , wherein Base is thymine.
11. The oligonucleotide according to claim 2 , wherein Base is adenine.
12. The oligonucleotide according to claim 2 , wherein Base is guanine.
13. The oligonucleotide according to claim 1 wherein the oligonucleotide is 10-20 nucleotide units in length.
14. The oligonucleotide according to claim 1 wherein the oligonucleotide is 12-18 nucleotide units in length.
15. The oligonucleotide according to claim 1 wherein the oligonucleotide is 13, 14, 15, 16, 17 or 18 nucleotide units in length.
16. The oligonucleotide according to claim 2 wherein the oligonucleotide is 10-20 nucleotide units in length.
17. The oligonucleotide according to claim 2 wherein the oligonucleotide is 12-18 nucleotide units in length.
18. The oligonucleotide according to claim 2 wherein the oligonucleotide is 13, 14, 15, 16 or 17 nucleotide units in length.
19. A nucleotide of formula:
wherein X is O; one of the H in (CH 2 )n is replaced with a C 1-6 alkyl substituent; n is 1; and Base is independently selected from the group consisting of cytosine, methyl cytosine, uracil, thymine, adenine and guanine.
20. The nucleotide according to claim 19 , wherein one of the H in (CH 2 )n is replaced with methyl.
21. The nucleotide according to claim 20 , wherein Base is cytosine or methyl cytosine.
22. The nucleotide according to claim 20 , wherein Base is uracil.
23. The nucleotide according to claim 20 , wherein Base is thymine.
24. The nucleotide according to claim 20 , wherein Base is adenine.
25. The nucleotide according to claim 20 , wherein Base is guanine.
26. The nucleotide according to claim 21 , wherein Base is cytosine, or methyl cytosine.
27. The nucleotide according to claim 21 , wherein Base is uracil.
28. The nucleotide according to claim 21 , wherein Base is thymine.
29. The nucleotide according to claim 21 , wherein Base is adenine.
30. The nucleotide according to claim 21 , wherein Base is guanine.