The identity of the cell adhesive protein substrate affects the efficiency of adeno-associated virus reverse transduction.

Abstract

Delivering genes from surfaces, called substrate-mediated gene delivery or reverse transduction, is a useful method to achieve spatial localization of gene delivery. We tested the compatibility of adeno-associated virus (AAV) vectors with various cell adhesive proteins to mediate gene delivery from surfaces. Our studies demonstrate that AAV vectors can be successfully adsorbed on collagen I, elastin, and laminin substrates leading to robust gene delivery to overlying cells. Notably, AAV immobilization on laminin yields the highest efficiency of gene expression. This increased gene expression cannot be explained by increases in the levels of virus deposition, transcriptional activity of cells, or virus vector uptake into cells. Further refinement of our knowledge of AAV interactions with extracellular matrix proteins may have important implications in a variety of applications ranging from tissue engineering to in vivo gene therapy.