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).sub.0-1-(LNA/LNA*).sub.2-7-(DNA/RNA/LNA*).sub.4-14-(LNA/LNA-
*).sub.2-7-(DNA/RNA).sub.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.