Potent LNA oligonucleotides for the inhibition of HIF-1A expression

摘要

Disclosed is an LNA oligonucleotide consisting of the sequence: 5'- TsGsGscsasasgscsastscscsTsGsTsa -3', Wherein a capital letter designates a beta-D-oxy-LNA nucleotide analogue, a small letter designates a 2-deoxynucleotide, and subscript "s" designates a phosphorothioate link between neighbouring nucleotides/LNA nucleotide analogues. The LNA oligonucleotides are useful for modulating the expression of hypoxia-inducible factor-la (HIF-1a). Further disclosed is the use of the oligonucleotide in the manufacture of a medicament for treating cancer, inhibiting angiogenesis, inducing apoptosis, preventing cellular proliferation, and treating an angiogenic diseases such as diabetic retinopathy, macular degeneration (ARMD), psoriasis, and rheumatoid arthritis.