Antisense inhibition of laminin-8 expression to inhibit...

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid

Reexamination Certificate

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C435S091100, C435S325000, C435S375000, C536S023100, C536S024300, C536S024330, C536S024500

Reexamination Certificate

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07547511

ABSTRACT:
Using gene array technology, we observed that an increase of the α4 chain-containing Laminin-8 correlated with poor prognosis for patients with brain gliomas. We established that inhibition of Laminin-8 expression by a new generation of highly specific and stable antisense oligonucleotides (Morpholino™) against chains of Laminin-8 could slow or stop the spread of glioma. This was demonstrated in an in vitro model using human glioblastoma multiforme cell lines M059K and U-87MG co-cultured with normal human brain microvascular endothelial cells (HBMVEC). Using Western blot analysis and immunohistochemistry, we con-firmed that antisense treatment effectively blocked laminin-8 protein synthesis. Antisense oligonucleotides against both α4 and β1 chains of laminin-8 blocked significantly the invasion of co-cultures through Matrigel. The results show that Laminin-8 may not only contribute to glioma progression and recurrence as part of the neovascularization process but also by directly increasing the invasive potential of tumor cells.

REFERENCES:
patent: 2005/055980 (2005-06-01), None
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