MOLECULAR CONJUGATE VECTORS MEDIATE EFFICIENT GENE-TRANSFER INTO GASTROINTESTINAL EPITHELIAL-CELLS

Transfer of genes to the gastrointestinal epithelium would be advantag eous from investigational and therapeutic standpoints. Efficient trans fer of DNA to the intestinal epithelial cells, however, has been probl ematic with conventional viral and nonviral vectors. As an alternative , we have utilized molecular conjugate vectors to transfer DNA to ente rocytes via the receptor-mediated endocytosis pathway. We were able to achieve efficient transfection of transformed (Caco(2) cells) and non transformed gastrointestinal cells derived from neonatal piglets utili zing molecular conjugate vectors. Analysis of heterologous gene expres sion revealed that enterocytes could serve as a secretory cellular sou rce of alpha(1)-antitrypsin and factor IX. Transient expression of het erologous DNA persisted for up to 2 weeks following transfection. Our observations suggest that molecular conjugate vectors may represent a promising strategy in the transfer of genes to cells of the gastrointe stinal tract.