LIPOSOME-MEDIATED GENE-TRANSFER INTO THE RAT ESOPHAGUS

Background-Cancer of the oesophagus has so far eluded every attempt at pharmacological treatment. The recent advent of somatic gene therapy offers a new therapeutic approach to malignant tumours. Aim-To investi gate whether and hour gene transfer into the oesophagus can be achieve d. Methods-A LacZ reporter gene was used as marker and transferred int o the oesophagus of rats using cationic liposomes. Gene transfer was a chieved by either luminal instillation into a closed segment using a d ouble balloon catheter, or by intramural injection through a needle. E xpression of beta-galactosidase was monitored in the oesophagus and va rious control tissues by histochemistry, polymerase chain reaction (PC R), reverse transcriptase PCR, and Southern blotting. Results-Up to 10 0 days after in vivo gene transfer beta-galactosidase activity could b e demonstrated in the oesophagus. Following luminal application, the t ransgene was expressed in epithelial cells whereas intramural injectio n induced preferential expression in fibroblasts. Conclusion-In vivo g ene transfer into the oesophagus is feasible and safe, and the route o f administration largely determines cell type specificity. This novel approach will enable in vivo studies of growth, differentiation, and m alignant transformation in the oesophagus, and may open new avenues to the confinement of oesophageal malignancies.