GENE-THERAPY OF THE GUT - INTRODUCTION OF THE APC TUMOR-SUPPRESSOR GENE FOR CANCER PREVENTION OR TREATMENT

Liposomal delivery of gene therapy to the colonic epithelium has been evaluated in a rodent model. The use of beta-galactosidase as a report er gene demonstrated uptake and expression in virtually 100% of the ep ithelial cells which contacted the liposome-gene mixture. Expression w as transient, persisting for 2-3 days, diminishing in accordance with normal epithelial turnover. Similar results were seen in both rats and mice. The method was used to deliver the APC tumor suppressor gene to rat colonic epithelium. Expression of RNA was verified by means of RN Ase protection, as well as by an exon-connection strategy utilizing re verse-transcription. A 6-week period of bi-weekly retreatment establis hed safety and minimal toxicity of this route; in particular, there we re no obvious changes in cell growth or differentiation with prolonged administration of the APC gene. The potential use of this method for delivery of gene therapy, and the specific application of the APC gene for cancer prevention or treatment, are discussed.