OLIGONUCLEOTIDOS DE LNA Y EL TRATAMIENTO DEL CANCER.

摘要

The present disclosure concerns LNA oligonucleotides having a (sub)sequence of the general formula 5'- ( Me Cx )(Tx,) Me CXAs Astscscsastsgsgs MeCXAX (G x) (c)-3',and preferably of the general formula 5'- Me C XTX), MeCXAsastscscsastsgsgs Me CxAx G x c-3', wherein capital letters designate a n LNA nucleotide analogue selected from .beta. -D-oxy-LNA, .beta. -D-thio-LNA, .beta.-D-amino-LNA and a-L-oxy-LNA, small letters designate a deoxynucleotid e, and underline 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 in vivo. The LNA oligonucleotides are superior to other L NA oligonucletides targeting Surviving mRNA measured by functional read outs su ch 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.