摘要 |
The present disclosure relates to an LNA oligonucleotide consisting of a sequence selected from the group consisting of 5'-(T x GxGxcsasasasgscsastscscsTXGX T-3' and 5'-(G X )TXTXascstsgscscststscsTXTX A- 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-la (HIF-1a), e.g. in t he 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. |