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 - 115 . (canceled)
116 . A method for the treatment of nephropathy or hypertension, wherein the method comprises administering to a subject in need of treatment, a nucleic acid that inhibits the signalling between SDF-1 and the SDF-1 receptor.
117 . The method according to claim 116 , wherein said nephropathy comprises diabetic nephropathy.
118 . The method according to claim 116 , wherein the nucleic acid comprises an SDF-1 binding molecule or an SDF-1 receptor binding molecule.
119 . The method according to claim 118 , wherein the SDF-1 binding molecule or the SDF-1 receptor binding molecule is selected from the group consisting of an aptamer, a Spiegelmer, an antibody and a small molecule.
120 . The method according to claim 118 , wherein the SDF-1 binding molecule or the SDF-1 receptor binding molecule is selected from the group consisting of a type A nucleic acid, a type B nucleic acid, a type C nucleic acid, SEQ ID NO:142, SEQ ID NO: 143 and SEQ ID NO:144,
wherein the type A 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 nucleic acid comprises a core nucleotide sequence:
(SEQ ID NO: 57)
5′ GUGUGAUCUAGAUGUADWGGCUGWUCCUAGUYAGG 3′
and
wherein the type C nucleic acid comprises a core nucleotide sequence:
(SEQ ID NO: 90)
5′ GGUUYAGGGCUHRX A AGUCGG 3′,
wherein X A is either absent or is A.
121 . The method according to claim 120 , wherein the
the type A nucleic acid comprises a nucleotide sequence according to any one of SEQ ID NOs:5 to 18, 25 to 41, 133, 137, 139, 140 or 141;
the nucleic type B acid comprises a nucleotide sequence according to any one of SEQ ID NOs:46 to 56, 61 to 72 or 132; and
the type C nucleic acid comprises a nucleotide sequence according to any one of SEQ ID NOs:79 to 89, 94 to 119, 134, 135 or 136.
122 . The method according to claim 116 , wherein the nucleic acid comprises an antagonist of the SDF-1 receptor system, wherein the SDF-1 receptor of the SDF-1 receptor system comprises CXCR4 or CXCR7.
123 . The method according to claim 116 , wherein the SDF-1 is a human SDF-1 or the SDF-1 receptor is a human SDF-1 receptor.
124 . The method according to claim 116 , wherein the nucleic acid comprises a modification.
125 . The method according to claim 124 , wherein the modification is selected from the group consisting of a HES moiety and a PEG moiety.
126 . The method according to claim 124 , 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.
127 . The method according to claim 116 , wherein the nucleic acid inhibits expression of SDF-1 or SDF-1 receptor and comprises siRNA molecules, ribozymes, antisense molecules or inhibitors of transcription factors.
128 . The method according to claim 116 , wherein said hypertension comprises pulmonary hypertension.
129 . A method for inhibiting the migration of leukocytes, wherein the method comprises administering to a subject in need of treatment a nucleic acid that inhibits signalling between SDF-1 and the SDF-1 receptor selected from the group consisting of a type A nucleic acid, a type B nucleic acid, a type C nucleic acid, SEQ ID NO:142, SEQ ID NO: 143 and SEQ ID N:144,
wherein the type A 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 nucleic acid molecule comprises a core nucleotide sequence:
(SEQ ID NO: 57)
5′ GUGUGAUCUAGAUGUADWGGCUGWUCCUAGUYAGG 3′;
and
wherein the type C nucleic acid molecule comprises a core nucleotide sequence of
(SEQ ID NO: 90)
GGUYAGGGCUHR X AAGUCGG,
wherein X A is either absent or is A.
130 . The method according to claim 129 , wherein the
the type A nucleic acid comprises a nucleotide sequence according to any one of SEQ ID NOs:5 to 18, 25 to 41, 133, 137, 139, 140 or 141;
the nucleic type B acid comprises a nucleotide sequence according to any one of SEQ ID NOs:46 to 56, 61 to 72 or 132; and
the type C nucleic acid comprises a nucleotide sequence according to any one of SEQ ID NOs:79 to 89, 94 to 119, 134, 135 or 136.
131 . The method according to claim 129 , wherein the nucleic acid comprises an antagonist of the SDF-1 receptor system, wherein the SDF-1 receptor of the SDF-11 receptor system comprises CXCR4 or CXCR7.
132 . The method according to claim 129 , wherein the SDF-1 is a human SDF-1 or the SDF-1 receptor of the SDF-1 receptor system is a human SDF-1 receptor.
133 . The method according to claim 129 , wherein the nucleic acid comprises a modification.
134 . The method according to claim 133 , wherein the modification is selected from the group consisting of a HES moiety and a PEG moiety.
135 . The method according to claim 133 , 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.