In vivo gene transfer methods in the bladder without viral vectors

• Published in: British Journal of Urology Vol. 81; no. 6; pp. 870 - 874
• Main Authors: HARIMOTO, K, SUGIMURA, K, LEE, C. R, KURATSUKURI, K, KISHIMOTO, T
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.06.1998; Blackwell
• Subjects: Animals; beta-Galactosidase - metabolism; Biological and medical sciences; Biomarkers; Biotechnology; bladder; Chloramphenicol O-Acetyltransferase - metabolism; Electroporation; Fundamental and applied biological sciences. Psychology; Gene therapy; Gene transfer; Gene Transfer Techniques; Health. Pharmaceutical industry; Industrial applications and implications. Economical aspects; liposome; Liposomes - administration & dosage; Male; Mice; particle gun; Rabbits; Rats; Respirovirus; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - therapy; Pulsed current; Microprojectile bombardment; Urinary system disease; Carcinoma; Liposome; Malignant tumor; Urinary tract disease; Experimental study; In vitro; Genetic transfer; Virus; Treatment; Urinary bladder; DNA; Bladder disease; Technique; Gene therapy; Matrix system
• ISSN: 0007-1331; 1464-410X
• DOI: 10.1046/j.1464-410x.1998.00644.x

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 β‐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.