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J Gen Virol. 2008 Dec;89(Pt 12):3004-8. doi: 10.1099/vir.0.2008/001446-0.

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

Author information

1
Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan, ROC.

Abstract

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.

PMID:
19008386
PMCID:
PMC3848193
DOI:
10.1099/vir.0.2008/001446-0
[Indexed for MEDLINE]
Free PMC Article

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