Enzon Pharmaceuticals, Inc.

Santaris Pharma A/s

Margit Wissenbach

Majken Westergaard

Kamille Dumong Petersen

Charlotte Albaek Thrue

Jens Bo Rode Hansen

Christoph Rosenbohm

Jens Bo Hansen

Charlotte Albæk Thrue

Lene Sonderbye Kjaerulff

Marlene Asklund

Bo Hansen

Lene Sønderbye Kjærulff

The present disclosure concerns LNA oligonucleotides having a (sub)sequence of the general formula 5'-()(T)CAtccatggCA()(c)-3&#x2032;, and preferably of the general formula 5&#x2032;-TCAatccatggCAc-3&#x2032;, wherein capital letters designate an LNA nucleotide analogue selected from &#x3b2;-D-oxy-LNA, &#x3b2;-D-thio-LNA, &#x3b2;-D-amino-LNA and &#x3b1;-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 tumor development in vivo. The LNA oligonucleotides are superior to other LNA oligonucleotides 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.

LNA oligonucleotides and the treatment of cancer

Oligonucleotides directed against the survivin gene are provided for modulating the expression of survivin. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the survivin. Methods of using these compounds for modulation of survivin expression and for the treatment of diseases associated with either overexpression of survivin, expression of mutated survivin or both are provided. Examples of diseases are cancer such as lung, breast, colon, prostate, pancreas, lung, liver, thyroid, kidney, brain, testes, stomach, intestine, bowel, spinal cord, sinuses, bladder, urinary tract or ovaries cancers. The oligonucleotides may be composed of deoxyribonucleosides or a nucleic acid analogue such as for example locked nucleic acid or a combination thereof.

Oligomeric compounds for the modulation of survivin expression

Growing community of inventors

Fredensborg, Denmark

Margit Wissenbach