Oligomeric compounds for the modulation HIF-1α expression
AssigneesEnzon Pharmaceuticals, Inc., Santaris Pharma A/S
InventorsCharlotte Albæk Thrue, Anja Mølhart Høg, Paul E. G. Kristjansen
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Abstract
Oligonucleotides directed against the hypoxia-inducible factor-1α (HIF-1α) gene are provided for modulating the expression of HIF-1α. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the HIF-1α. Methods of using these compounds for modulation of HIF-1α expression and for the treatment of diseases associated with the hypoxia-inducible factor-1α are provided. Examples of diseases are cancer and pre-eclampsia. The oligonucleotides may be composed of deoxyribonucleosides, a nucleic acid analogue, or Locked Nucleic Acid (LNA) or a combination thereof.
Claims35
A compound of 16 to 50 nucleotides or nucleotide analogues, wherein adjacent nucleotides or nucleotide analogues are covalently linked by an internucleotide linkage, which is capable of modulating HIF-1α as encoded by a nucleic acid molecule having the sequence of SEQ ID NO. 1 and wherein a region of said compound has a sequence that is identically present in SEQ ID NO:
- 55.
A compound of 16 to 50 nucleotides or nucleotide analogues, wherein adjacent nucleotides or nucleotide analogues are covalently linked by an internucleotide linkage, targeted to a nucleic acid molecule encoding HIF-1α (SEQ ID NO. 1), wherein said compound hybridizes with said nucleic acid molecule and is capable of inhibiting the expression of HIF-1α in a cell and wherein a region of said compound has a sequence that is identically present in SEQ ID NO:
- 55.
A compound represented by the formula:TsGsGsCsasasgscsastscscsTsGsTsA (SEQ ID NO. 55) wherein uppercase letters denote oxy-LNA nucleotides, lowercase letters denote deoxynucleotides and the subscript “s” denotes a phosphorothioate linkage.
A compound selected from TsGsGsCsasasgscsastscscsTsGsTsa (SEQ ID NO. 55) and tsGsGsCsasasgscsastscscsTsGsTsA (SEQ ID NO. 55) wherein uppercase letters denote oxy-LNA nucleotides, lowercase letters denote deoxynucleotides and the subscript “s” denotes a phosphorothioate linkage.
A compound of 16 to 50 nucleotides or nucleotide analogues, wherein adjacent nucleotides are covalently linked by an internucleotide linkage, which is capable of modulating HIF-1α as encoded by the nucleic acid molecule having the sequence of SEQ ID NO. 1, wherein said compound has a sequence that is complementary to the sequence of a target site located at nucleotides 1177 to 1192 of said nucleic acid molecule, and wherein said compound comprises at least one nucleotide analogue that is an LNA unit.
Dependencies are inferred from the claim text.