Abstract: The present disclosure concerns LNA oligonucleotides having a (sub)sequence of the general formula 5?-(MeCx)(Tx)MeCxAsAstsCsCsastsgsgsMeCxAx(Gx)(c)-3?, and preferably of the general formula 5?-MeCxTxMeCxAsastscscsastsgsgsMeCxAxGxc-3?, wherein capital letters designate an LNA nucleotide analogue selected from ?-D-oxy-LNA, ?-D-thio-LNA, ?-D-amino-LNA and ?-L-oxy-LNA, small letters designate a deoxynucleotide, 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.

Abstract: The present invention provides improved oligomeric compound, in particular oligonucleotide compounds, and methods for modulating the expression of the Bcl-2 gene in humans. In particular, this invention relates to oligomeric compounds of 10-30 nucleobases in length which comprise a target binding domain that is specifically hybridizable to a region ranging from base position No. 1459 (5?) to No. 1476 (3?) of the human Bcl-2 mRNA, said target binding domain having the formula: 5?-[(DNA/RNA)0-1-(LNA/LNA*)2-7-(DNA/RNA/LNA*)4-14-(LNA/LNA*)2-7-(DNA/RNA)0-1]-3? and said target binding domain comprising at least two LNA nucleotides or LNA analogue nucleotides linked by a phosphorothioate group (—O—P(O,S)—O—). In particular the oligo is predominantly or fully thiolated. The invention also provides the use of such oligomers or conjugates or chimera for the treatment of various diseases associated with the expression of the Bcl-2 gene, such as cancer.

Abstract: The present disclosure concerns LNA oligonucleotides having a (sub)sequence of the general formula 5?-(MeCx)(Tx)MeCxAsAstscscsastsgsgsMeCxAx)(Gx)(c)-3?, and preferably of the general formula 5?-MeCxTxMeCxAsastscscsastsgsgsMeCxAxGxc-3?, wherein capital letters designate an LNA nucleotide analogue selected from ?-D-oxy-LNA, ?-D-thio-LNA, ?-D-amino-LNA and ?-L-oxy-LNA, small letters designate a deoxynucleotide, 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.