Related Experiment Videos
Transrectal gene therapy of the prostate in the canine model
Kyle J Weld1, Brant E Mayher, James A Allay
1Urologic Research Laboratories, University of Tennessee, Memphis, Tennessee 38163, USA.
Abstract:
Direct transrectal delivery of therapeutic genes utilizing adenoviral vectors for advanced prostate cancer may offer effective treatment at the molecular level. Large animal models to assess feasibility and the intraprostatic and systemic dissemination patterns of these vectors have not been reported. For these studies, a replication-deficient (E1(-)/E3(-)) recombinant adenovirus (AdRSVlacZ) expressing bacterial beta-galactosidase (beta-gal) was delivered under transrectal ultrasound guidance. Two prostate biopsies, followed by concurrent injection of 4.8 x 10(9) pfu of the adenoviral vector divided into either 1 or 2 mL of diluent, were performed (n=4). Swabs of the rectum, sputum, and urine were collected and after 72 hours, the animals were sacrificed. Specimens were assayed for the presence of virus and beta-gal activity. Rectal swabs were transiently positive, whereas urine and sputum samples showed no detectable vector throughout the experiment. Beta-gal activity was observed at the prostate injection sites with detectable activity noted up to 7.5 mm away from the injection site. Systemic dissemination was observed regardless of the injected volume. In conclusion, transrectal prostate biopsy with concurrent prostate injection is a feasible method to deliver therapeutic adenoviral vectors for the treatment of prostate cancer; however, systemic distribution and temporary rectal shedding of virus should be anticipated.
Insights
Transrectal delivery of adenoviral vectors via prostate biopsy shows feasibility for prostate cancer gene therapy. While effective locally, anticipate temporary rectal shedding and systemic virus distribution.
Area of Science:
- Oncolytic virology
- Gene therapy delivery systems
- Prostate cancer research
Background:
- Advanced prostate cancer necessitates novel molecular-level treatments.
- Adenoviral vectors offer potential for targeted gene delivery.
- Feasibility and dissemination patterns of transrectal adenoviral vector delivery in large animals remain uncharacterized.
Purpose of the Study:
- To assess the feasibility of direct transrectal adenoviral vector delivery into the prostate.
- To investigate intraprostatic and systemic dissemination patterns of adenoviral vectors in a large animal model.
Main Methods:
- Replication-deficient recombinant adenovirus (AdRSVlacZ) expressing beta-galactosidase was administered via transrectal ultrasound-guided prostate biopsy and injection.
- Adenoviral vector (4.8 x 10(9) pfu) was delivered in 1 or 2 mL diluent to four animals.
- Rectal, sputum, and urine samples were collected 72 hours post-injection; animals were then sacrificed for tissue analysis.
Main Results:
- Transiently positive rectal swabs were detected; urine and sputum remained negative for vector.
- Beta-galactosidase activity was confirmed at prostate injection sites, extending up to 7.5 mm.
- Systemic virus dissemination occurred irrespective of injected diluent volume.
Conclusions:
- Transrectal prostate biopsy with concurrent injection is a viable method for delivering adenoviral vectors for prostate cancer.
- Potential challenges include anticipated systemic virus distribution and temporary rectal shedding.