ADENOVIRUS-MEDIATED TRANSDUCTION OF RIBOZYMES ABROGATES HER-2 NEU ANDPLEIOTROPHIN EXPRESSION AND INHIBITS TUMOR-CELL PROLIFERATION/

The combination of specific gene targeting technologies with efficient gene delivery systems could provide the to evaluate the concept of an ticancer strategies ed to block expression of potentially rate-limitin g tumor promoting factors. Here, we constructed adenoviruses expressin g hammerhead-ribozymes targeted to two of these factors, the tyrosine kinase receptor HER-2/neu or the growth factor pleiotrophin (PTN). Ade novirus-mediated transduction of either HER-2/neu- or PTN-targeted rib ozymes depleted the respective RNAs and inhibited protein expression s ignificantly in three different human cancer cell lines. This resulted in almost complete abrogation of HER-2/neu- or PTN-dependent cancer-c ell proliferation, thus demonstrating the feasibility of this approach as a future cancer gene therapy.