Adenovirus–Microbead Conjugates Possess Enhanced Infectivity: A New Strategy for Localized Gene Delivery

AbstractWe have created a novel method for coupling adenoviral vectors to solid microbeads in a way that does not adversely affect the infectivity of the attached virions. This method utilizes the extremely tight interaction between the protein streptavidin and its ligand biotin as a means of tethering viral particles to microbeads. The adenovirus–microbead conjugates that were created functioned as fully infectious entities and possessed several functional advantages over free, unmodified viral particles. The adenovirus–microbead conjugates possessed enhanced ability to transduce target cells in culture. For target cells of a highly permissive nature, this increase in infectivity was modest. However for target cells of moderate to low permissivity, the enhancement of transduction efficiency was substantial. Adenoviral vectors, previously incapable of infecting a particular colon cancer cell line, were made fully infectious on the same cell line when delivered as solid-phase conjugates. Additionally, solid-phase adenovirus–microbead conjugates showed highly limited diffusion in solution, allowing for focused delivery of viral vectors only to cells that come into contact with the conjugates. When the solid phase to which the viral particles were attached had paramagnetic properties, the location of viral infections was tightly controllable by magnetic force through the use of strategically placed magnets