Transport across a polarized monolayer of Caco-2 cells by transferrin receptor-mediated adenovirus transcytosis

Zeng B. Zhu, Sharmila K. Makhija, Baogen Lu, Minghui Wang, Angel A. Rivera, Meredith Preuss, Fen Zhou, Gene P. Siegal, Ronald D. Alvarez, David T. Curiel

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Adenoviral vectors have a poor record of transgene delivery efficiency through physical barriers such as the epithelium or endothelium. We report here the construction of an adenoviral vector that has the capability to be transported across polarized epithelial monolayers of Caco-2 cells (a colon carcinoma cell line) by transcytosis. This transcytosis is transferrin receptor (TfR)-mediated with use of a bifunctional adaptor, soluble coxsackie adenovirus receptor (sCAR)-Tf, and is both temperature and iron dependent. Under experimental conditions, the adenoviral transcytosis was inhibited by pretreatment of Caco-2 cells with colchicine, an inhibitor of transcytosis, and was not enhanced by pretreatment with Brefeldin A (BFA), an enhancer of transcytosis. In these Caco-2 cells, the transcytosis rate was 0.3 ± 1.3% (SD). The transcytosed adenoviruses remain biologically functional. These data suggest the potential clinical benefit under conditions where drug delivery is a challenge, such as within the airway epithelium, at the bladder lumen urothelial cell interface, and across the blood-brain barrier for clinical treatment of lung, urogenital, and brain disorders, respectively, by adenoviral transcytosis of transgene delivery.

Original languageEnglish (US)
Pages (from-to)116-128
Number of pages13
JournalVirology
Volume325
Issue number1
DOIs
StatePublished - Jul 20 2004
Externally publishedYes

Keywords

  • Adenovirus
  • CMV
  • Caco-2 cells
  • Tf
  • TfR
  • base pairs
  • bp
  • cytomegalovirus
  • transferrin
  • transferrin receptor
  • viral particles
  • vp

ASJC Scopus subject areas

  • Virology

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  • Cite this

    Zhu, Z. B., Makhija, S. K., Lu, B., Wang, M., Rivera, A. A., Preuss, M., Zhou, F., Siegal, G. P., Alvarez, R. D., & Curiel, D. T. (2004). Transport across a polarized monolayer of Caco-2 cells by transferrin receptor-mediated adenovirus transcytosis. Virology, 325(1), 116-128. https://doi.org/10.1016/j.virol.2004.04.021