Bovine AAV transcytosis inhibition by tannic acid results in functional expression of CFTR in vitro and altered biodistribution in vivo

Gene Ther. 2012 May;19(5):576-81. doi: 10.1038/gt.2011.138. Epub 2011 Oct 20.

Abstract

Bovine adeno-associated virus (BAAV) can enter a cell either through a transcytosis or transduction pathway. We previously demonstrated that particles entering via the transcytosis pathway can be redirected to transduce the cell by blocking particle exocytosis with tannic acid (TA). To investigate whether this approach is useful in lung gene therapy applications, we tested the effect of TA on BAAV transduction in cystic fibrosis airway epithelia in vitro, and in mouse lung in vivo. Our findings suggest that BAAV transcytosis can occur in vivo and that treatment with TA reduces transcytosis and increases lung transduction. TA treatment did not impair the sorting and the activity of the BAAV expressed cystic fibrosis transmembrane regulator membrane protein.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Dependovirus / genetics
  • Gene Transfer Techniques
  • Genetic Vectors
  • Mice
  • Respiratory Mucosa / metabolism
  • Tannins / pharmacology*
  • Tissue Distribution
  • Transcytosis*

Substances

  • Tannins
  • Cystic Fibrosis Transmembrane Conductance Regulator