TARGETING GENE-THERAPY VECTORS TO CNS MALIGNANCIES

Gene therapy offers significant advantages to the field of oncology wi th the addition of specifically and uniquely engineered mechanisms of halting malignant proliferation through cytotoxicity or reproductive a rrest. To confer a true benefit to the therapeutic ratio (the relative toxicity to tumor compared to normal tissue) a vector or the transgen e it carries must selectively affect or access tumor cells. Beyond the selective toxicities of many transgene products, which frequently par allel that of contemporary chemotherapeutic agents, lies the potential utility of targeting the vector. This review presents an overview of current and potential methods for designing vectors targeted to CNS ma lignancies through selective delivery, cell entry, transport or transc riptional regulation. The topic of delivery encompasses physical and p harmaceutic means of increasing the relative exposure of tumors to vec tor, Cell entry based methodologies are founded on increasing relative uptake of vector through the chemical or recombinant addition of liga nd and antibody domains which selectively bind receptors expressed on target cells. Targeted transport involves the potential for using cell s to selectively carry vectors or transgenes into tumors. Finally, pro moter and enhancer systems are discussed which have potential for sele ctivity activating transcription to produce targeted transgene express ion or vector propagation.