SDF-1 binding nucleic acids and the use thereof
The present invention is related to a nucleic acid molecule binding to SDF-1, whereby the nucleic acid molecule influences migration of cells.
1. A method for the treatment of nephropathy or hypertension, wherein the method comprises administering to a subject in need of treatment, an L-nucleic acid that inhibits signalling between SDF-1 and an SDF-1 receptor,
wherein the L-nucleic acid comprises an SDF-1 binding molecule selected from the group consisting of a type A L-nucleic acid, a type B L-nucleic acid, a type C L-nucleic acid, SEQ ID NO:142, SEQ ID NO:143 and SEQ ID NO:144,
wherein the type A L-nucleic acid comprises a core nucleotide sequence:
(SEQ ID NO: 19)
5′ AAAGYRACAHGUMAAX A UGAAAGGUARC 3′
wherein X A is either absent or is A,
wherein the type B L-nucleic acid comprises a core nucleotide sequence:
(SEQ ID NO: 57)
5′ GUGUGAUCUAGAUGUADWGGCUGWUCCUAGUYAGG 3′
and
wherein the type C L-nucleic acid comprises a core nucleotide sequence:
(SEQ ID NO: 90)
5′ GGUYAGGGCUHRX A AGUCGG 3′,
wherein X A is either absent or is A;
and said SDF-1 receptor comprises CXCR4 or CXCR7.
2. The method according to claim 1 , wherein said nephropathy comprises diabetic nephropathy.
3. The method according to claim 1 , wherein
the type A L-nucleic acid comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs:5 to 18, 25 to 41, 133, 137, 139, 140 and 141;
the type B L-nucleic acid comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs:46 to 56, 61 to 72 and 132; and
the type C L-nucleic acid comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs:79 to 89, 94 to 119, 134, 135 and 136.
4. The method according to claim 1 , wherein the SDF-1 is a human SDF-1 or the SDF-1 receptor is a human SDF-1 receptor.
5. The method according to claim 1 , wherein the L-nucleic acid comprises a modification.
6. The method according to claim 5 , wherein the modification is selected from the group consisting of a HES moiety and a PEG moiety.
7. The method according to claim 5 , wherein the modification comprises a PEG moiety consisting of a straight or branched PEG, wherein the molecular weight of the PEG moiety is from about 2 to 180 kD, 60 to 140 kD or about 40 kD.
8. The method according to claim 1 , wherein said hypertension comprises pulmonary hypertension.
9. A method for inhibiting the migration of leukocytes, wherein the method comprises administering to a subject in need of treatment an L-nucleic acid that inhibits signalling between SDF-1 and an SDF-1 receptor,
wherein said L-nucleic acid comprises an SDF-1 binding molecule selected from the group consisting of a type A L-nucleic acid, a type B L-nucleic acid, a type C L-nucleic acid, SEQ ID NO:142, SEQ ID NO:143 and SEQ ID N:144,
wherein the type A L-nucleic acid comprises a core nucleotide sequence:
(SEQ ID NO: 19)
5′ AAAGYRACAHGUMAAX A UGAAAGGUARC 3′
wherein X A is either absent or is A,
wherein the type B L-nucleic acid molecule comprises a core nucleotide sequence:
(SEQ ID NO: 57)
5′ GUGUGAUCUAGAUGUADWGGCUGWUCCUAGUYAGG 3′;
and
wherein the type C L-nucleic acid molecule comprises a core nucleotide sequence of
(SEQ ID NO: 90)
GGUYAGGGCUHRX A AGUCGG,
wherein X A is either absent or is A,
and said SDF-1 receptor comprises CXCR4 or CXCR7.
10. The method according to claim 9 , wherein
the type A L-nucleic acid comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs:5 to 18, 25 to 41, 133, 137, 139, 140 and 141;
the type B L-nucleic acid comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs:46 to 56, 61 to 72 and 132; and
the type C L-nucleic acid comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs:79 to 89, 94 to 119, 134, 135 and 136.
11. The method according to claim 9 , wherein the SDF-1 is a human SDF-1 or the SDF-1 receptor is a human SDF-1 receptor.
12. The method according to claim 9 , wherein the L-nucleic acid comprises a modification.
13. The method according to claim 12 , wherein the modification is selected from the group consisting of a HES moiety and a PEG moiety.
14. The method according to claim 12 , wherein the modification comprises a PEG moiety consisting of a straight or branched PEG, wherein the molecular weight of the PEG moiety is from about 2 to 180 kD, from about 60 to 140 kD or about 40 kD.