HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplementary Material Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Fu, Y.-Y. Articles by Tang, S.-C. Search for Related Content PubMed PubMed Citation Articles by Fu, Y.-Y. Articles by Tang, S.-C. Agricola Articles by Fu, Y.-Y. Articles by Tang, S.-C.

Transient cytochalasin-D treatment induces apically administered rAAV2 across tight junctions for transduction of enterocytes

¹ Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan, ROC
² Division of Pediatric Gastroenterology, Stanford University School of Medicine, Stanford, CA 94305, USA

Correspondence
Shiue-Cheng Tang
sctang{at}che.nthu.edu.tw

Enteropathogens are known to disrupt apical actin filaments and/or tight-junction barriers of intestinal epithelial cells to promote infection. In this study, we show that a controlled, cytochalasin-D (Cyto-D)-mediated disruption of actin filaments and tight junctions enhanced the apical delivery of the gene-therapy vector recombinant adeno-associated virus serotype 2 (rAAV2). This increase in transduction efficiency can be attributed to the enhanced delivery of rAAV2 across the Cyto-D disrupted tight junctions, allowing basolateral entry of rAAV2. Previously, we have shown that MG101 and doxorubicin are capable of overcoming proteasome-mediated transduction barriers of rAAV2 in enterocytes. In this study, when Cyto-D was combined with MG101 and doxorubicin in apical delivery of rAAV2 to transduce the differentiated Caco-2 enterocytes, a synergistic >2300-fold increase in transgene expression was achieved. We conclude that Cyto-D is capable of permeating the polarized enterocytes for rAAV2 transduction, which may potentially be a useful device to facilitate intestinal gene transfer via the gut lumen.

Supplementary figures are available with the online version of this paper.