| 摘要 |
<p>The present disclosure concerns LNA oligonucleotides having a (sub)sequence of the general formula <sub>5'- (</sub> <sup>Me</sup> <sub/> <sub>Cx</sub> <sub>)(Tx,)</sub> <sup>Me</sup> <sub/>C<sub>X</sub>A<sub>s</sub> <u>As</u>t<sub>s</sub>c<sub>s</sub>c<sub>s</sub>a<sub>s</sub>t< sub>s</sub>g<sub>s</sub>g<sub>s</sub> <sup>Me</sup>C<sub>X</sub>A<sub>X</sub> (<u>G</u> <sub>x)</sub> (<sup/>c)-3',<sub/>and preferably of the general formula 5'<sup>- Me</sup> <u>C</u> <sub>X</sub>T<sub>X</sub>),<sup>Me</sup>C<sub>X</sub>A<sub>s</s ub>a<sub>s</sub>t<sub>s</sub>c<sub>s</sub>c<sub>s</sub>a<sub>s</ sub>t<sub>s</sub>g<sub>s</sub>g<sub>s</sub> <sup>Me</sup> <sub/>C<sub>x</sub>A<sub>x</sub> <u>G</u> <sub>x</sub> c-3', wherein capital letters designate an LNA nucleotide analogue selected from ???? -D-oxy-LNA, ???? -D-thio-LNA, ????-D-amino-LNA and a-L-oxy-LNA, small letters designate a deoxynucleotide, and <u>underline</u> designates either an LNA nucleotide analogue as defined above or a deoxynucleotide. Such LNA oligonucleotides exhibit surprisingly good properties with respect to inhibition of the expression of Survivin by means of an anti-sense mechanism, and thereby lead to reduction or inhibition of tumour development <i>in vivo.</i>The LNA oligonucleotides are superior to other LNA oligonucletides targeting Surviving mRNA measured by functional read outs such as apoptosis induction and proliferation inhibition, and is potent in down-regulating Survivin mRNA and protein in transfected cancer cell lines, and induce apoptosis in combination with Taxol superior compared to other LNA oligonucleotides.</p> |
