| abstract |
The present disclosure relates to LNA oligonucleotides having a (sub) sequence of the general formula 5 - (MeCx) (Tx,) MeCxAsAstscscsastsgsgsMeCxAx (Gx) (c) -3 ??, and preferably of the general formula 5 ?? - MeCxTx), MeCxAsastscscsastsgsgs MeCxAx Gx c-3 ??, where the capital letters designate an analogue of the LNA nucleotide selected from ?? - D-oxi-LNA, ?? - D-uncle-LNA, ?? - D- amino-LNA and aL-oxy-LNA, the lowercase designate a deoxyunucleotide, and the underlined designates either an analogue of the LNA nucleotide as defined above, or a deoxynucleotide. These LNA oligonucleotides exhibit surprisingly good properties with respect to the inhibition of Survivin expression through an anti-sense mechanism, and thereby lead to the reduction or inhibition of tumor development in vitro. The LNA oligonucleotides are superior to other LNA oligonucleotides that target Survivin mRNA measured by reading outputs such as, for example, induction of apoptosis and inhibition of proliferation, and is potent to sub-regulate Survivin mRNA and protein in cancer cell lines transfected, and induce apoptosis in combination with Taxol superior compared to other LNA oligonucleotides. |