Delivery of adenoviral vectors to the prostate for gene therapy

Prostate cancer has become the most frequently occurring cancer and the sec ond leading cause of cancer deaths in men. One novel approach to combat pro state cancer is gene therapy. A replication-deficient recombinant adenovira l vector (AdRSVlacZ) expressing bacterial beta-galactosidase (beta-gal) (la cZ) under the control of the Rous sarcoma virus promoter was used to determ ine which delivery route was best for the transduction of adenoviral vector s to the prostate. Using a canine model, adenoviral vectors were administer ed by intravenous, intra-arterial, and intraprostatic (i.p.) injections. Af ter injections, the expression of the lacZ gene was measured in canine pros tates as well as in various other organs to determine the distribution of t he disseminated adenoviral vector by (a) the percentage of cells expressing lacZ in situ (5-bromo-4-chloro-3-indolyl beta-D-galactoside staining), (b) beta-gal enzymatic activity (colorimetric beta-gal assay), and (c) polymer ase chain reaction of genomic DNA using primers specific for the adenoviral genome. An i.p. injection of the adenoviral vector resulted in a greater t ransduction rate and expression level of lacZ in the prostate than either i ntravenous or intra-arterial (inferior vesical/prostatic artery) injections . Thus, an i.p. (or intratumoral) injection seems to be the best route to t reat local regional prostate cancer by viral-based gene therapy.