) It is the goal of this proposal to facilitate gene therapy for neoplastic diseases by developing a vector capable of efficient and cell-specific gene delivery. It is our hypothesis that genetic modifications can be made to the adenoviral vector to alter its native viral tropism in order to achieve selective transduction by target tumor cells. To this end, our specific aims are to define peptides which exhibit specific binding to target tumor cells for employment in adenoviral vector retargeting approaches; to develop methods to display tumor binding peptides in hexon capsid protein of adenovirus in the context of vector retargeting approaches; to demonstrate tumor specific gene delivery via adenoviral vectors modified to contain tumor binding peptides within modified hexon proteins; and to prepare and validate novel adenoviral vectors employing these retargeting principles for human clinical gene therapy trials in the context of cancer of the ovary. By addressing the key issue which limits the translation of present gene therapy strategies into clinical trials, the development of this vector system would represent a major technical advance in gene therapy for neoplastic diseases.
NOT AVAILABLE
