POTENT LNA OLIGONUCLEOTIDES FOR THE INHIBITION OF HIF-1A EXPRESSION
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Abstract
The present disclosure relates to an LNA oligonucleotide consisting of a sequence selected from the group consisting of 5′-(Tx)GxGxcsasasgscsastscscsTxGxT-3′ and 5′-(Gx)TxTxascstsgscscststscsTxTxA-3′, wherein capital letters designate a beta-D-oxy-LNA nucleotide analogue, small letters designate a 2-deoxynucleotide, underline designates either a beta-D-oxy-LNA nucleotide analogue or a 2-deoxynucleotide, subscript “s” designates a phosphorothioate link between neighbouring nucleotides/LNA nucleotide analogues, and subscript “x” designates either a phosphorothioate link or a phosphorodiester link between neighbouring nucleotides/LNA nucleotide analogues, and wherein the sequence is optionally extended by up to five 2-deoxynucleotide units. The LNA oligonucleotides are useful for modulating the expression of hypoxia-inducible factor-1a (HIF-1a), e.g. in the treatment of cancer diseases, inhibiting angiogenesis, inducing apoptosis, preventing cellular proliferation, or treating an angiogenic disease, e.g. diabetic retinopathy, macular degeneration (ARMD), psoriasis, rheumatoid arthritis and other inflammatory diseases.
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1-30. -30. (canceled)
- 31. A method for treating liver cancer, the method comprising administering to a liver-cancer patient a composition comprising a therapeutically effective amount of the LNA oligonucleotide
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