VIRAL AND NONVIRAL GENE DELIVERY VECTORS FOR CANCER GENE-THERAPY

The development of vectors that are capable of efficient gene delivery is crucial to the success of gene therapy. We have developed both rec ombinant viral and nonviral vectors with the goal of correcting geneti c abnormalities in cancer cells that are responsible for malignant tra nsformation. Infection of cancer cells by recombinant adenovirus (Adv) indicates that the level of transduction is variable and dependent on the virus-to-cell ratio. Infection of cells with Adv/p53 resulted in levels of tumor suppressor p53 gene expression that could mediate tumo r cell growth suppression and apoptosis, both in vitro and in vivo. Th e treatment of cancer cells with cisplatin prior to Adv transduction r esulted in a higher level of therapeutic gene expression. Epidermal gr owth factor (EGF)/DNA complexes targeted to cancer cells overexpressin g the EGF receptor resulted in efficient transduction of several lung cancer cell lines in vitro. As a result, these vectors provide improve d methods with which to treat cancer in the clinical setting with gene therapy.