OBJECTIVE: To examine three in vivo gene transfer methods, without viral vectors, for use in bladder cancer. MATERIALS AND METHODS: Three methods were selected: (i) haemagglutinating virus of Japan (HVJ)-liposomes possessing membrane fusion activity were intraluminally injected into rat bladders; (ii) using a particle gun, rabbit bladder mucosa was bombarded with DNA-coated gold microcarriers; (iii) electrotransfection was also assessed in rabbit bladder by pulsed direct currents (0.15-0.2 A, 50 ms, repeated eight times) generated between needle electrodes after the submucosal injection of DNA solution. The beta-galactosidase gene and chloramphenicol acetyl-transferase gene were used as marker genes to detect gene transfer. RESULTS: HVJ liposomes efficiently transfected superficial layers of urothelium, with a peak of expression on day 5. The particle gun produced a heterogeneous but efficient transfection in deeper layers of the urothelium. By electrotransfection, both submucosal interstitial cells and urothelium were transfected. No major complications occurred with these three methods. CONCLUSION: HVJ-liposomes are potentially useful for treating carcinoma in situ. With further refinement, the last two methods may be suitable for adjuvant therapy in treating localized bladder tumours.
OBJECTIVE: To examine three in vivo gene transfer methods, without viral vectors, for use in bladder cancer. MATERIALS AND METHODS: Three methods were selected: (i) haemagglutinating virus of Japan (HVJ)-liposomes possessing membrane fusion activity were intraluminally injected into rat bladders; (ii) using a particle gun, rabbit bladder mucosa was bombarded with DNA-coated gold microcarriers; (iii) electrotransfection was also assessed in rabbit bladder by pulsed direct currents (0.15-0.2 A, 50 ms, repeated eight times) generated between needle electrodes after the submucosal injection of DNA solution. The beta-galactosidase gene and chloramphenicol acetyl-transferase gene were used as marker genes to detect gene transfer. RESULTS: HVJ liposomes efficiently transfected superficial layers of urothelium, with a peak of expression on day 5. The particle gun produced a heterogeneous but efficient transfection in deeper layers of the urothelium. By electrotransfection, both submucosal interstitial cells and urothelium were transfected. No major complications occurred with these three methods. CONCLUSION: HVJ-liposomes are potentially useful for treating carcinoma in situ. With further refinement, the last two methods may be suitable for adjuvant therapy in treating localized bladder tumours.