Potent LNA oligonucleotides for the inhibition of HIF-1A expression
First Claim
1. 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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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 analog, small letters designate a 2-deoxynucleotide, underline designates either a beta-D-oxy-LNA nucleotide analog or a 2-deoxynucleotide, subscript “s” designates a phosphorothioate link between neighboring nucleotides/LNA nucleotide analogs, and subscript “x” designates either a phosphorothioate link or a phosphorodiester link between neighboring nucleotides/LNA nucleotide analogs, 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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12 Claims
- 1. 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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