Methods and compositions for increasing the infectivity of gene transfer vectors

A method for expressing a polypeptide in cells of an epithelial tissue comprising:

• (a) providing a packaged viral vector comprising a polynucleotide encoding said polypeptide;
• (b) increasing the permeability of said epithelial tissue by treating said tissue with a hypotonic solution and/or a chelator of divalent cations;
• and
• (c) contacting cells of the permeabilized epithelial tissue with said packaged viral vector under conditions permitting the uptake of said packaged viral vector by said cells and expression of said polypeptide therein;
• whereby increased permeability of said epithelial tissue facilitates improved viral transduction of said cells, which in turn facilitates expression of said polypeptide.

A method of increasing transport of chloride ions in airway epithelial tissue of a mammal suffering from cystic fibrosis comprising:

• a) providing a packaged viral vector comprising a polynucleotide encoding a cystic fibrosis transmembrane regulator (CFTR) protein;
• b) contacting said airway epithelial tissue with a hypotonic solution and/or a chelator of divalent cations in a sufficient amount to produce permeabilized epithelial tissue;
• and
• c) contacting cells of said permeabilized airway epithelial tissue with said packaged viral vector under conditions permitting uptake of the packaged viral vector by said cells, and expression of said CFTR protein therein;
• wherein a sufficient quantity of said CFTR protein is produced to increase chloride ion transport in the airway epithelial tissue.