The liberation of CD44 intracellular domain modulates adenoviral vector transgene expression.

ABSTRACT: The success of gene therapy in the ocular environment is partly due to the presence of hyaluronan in vitreous. Here we explore the mechanism of hyaluronan-mediated enhancement of adenoviral vector transgene expression. Introduction of hyaluronan receptor CD44 into CD44-negative cells followed by transduction in the presence of vitreous with an adenoviral vector containing an IL-12-coding transgene increases IL-12 secretion. We demonstrate that sequential CD44 proteolysis is responsible for hyaluronan-mediated enhancement. Metalloproteinase or γ-secretase inhibitors decrease adenoviral-mediated transgene expression. Deletion of these proteolytic sites in CD44 also inhibits transgene expression. Expression of CD44 with a mutation to prevent phosphorylation of serine 325 inhibits the response

SUBMITTER: Ildefonso CJ 

PROVIDER: S-EPMC3463356 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature