In vivo gene transfer methods in the bladder without viral vectors

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Abstract
To examine three in vivo gene transfer methods, without viral vectors, for use in bladder cancer. 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 β-galactosidase gene and chloramphenicol acetyl-transferase gene were used as marker genes to detect gene transfer. 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. 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.