Molecular conjugate vectors mediate efficient gene transfer into gastrointestinal epithelial cells.
Transfer of genes to the gastrointestinal epithelium would be advantageous from investigational and therapeutic standpoints. Efficient transfer of DNA to the intestinal epithelial cells, however, has been problematic with conventional viral and nonviral vectors. As an alternative, we have utilized molecular conjugate vectors to transfer DNA to enterocytes via the receptor-mediated endocytosis pathway. We were able to achieve efficient transfection of transformed (Caco2 cells) and nontransformed gastrointestinal cells derived from neonatal piglets utilizing molecular conjugate vectors. Analysis of heterologous gene expression revealed that enterocytes could serve as a secretory cellular source of alpha 1-antitrypsin and factor IX. Transient expression of heterologous 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 gastrointestinal tract.
Batra
R K
RK
Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, USA.
Berschneider
H
H
Curiel
D T
DT
D000230:Adenocarcinoma / Q000473:pathology; D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000473:pathology; D004274:DNA, Recombinant / Q000235:genetics; D004705:Endocytosis; D004847:Epithelial Cells; D005347:Fibroblasts / Q000166:cytology; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology*; D007583:Jejunum / Q000166:cytology; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D011107:Polylysine; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013552:Swine; D014162:Transfection; D014168:Transferrin; D014407:Tumor Cells, Cultured
D004274:DNA, Recombinant; D011993:Recombinant Fusion Proteins; D014168:Transferrin; D011107:Polylysine; D008156:Luciferases