Poly(lactic-glycolic) acid copolymer encapsulation of recombinant adenovirus reduces immunogenicity in vivo

Adenovirus-mediated gene transfer has application to the treatment of diseases of the central nervous system. We demonstrate that a limitation to its use in vivo is an inability lo redose to the brain. We show that one factor inhibiting re-dosing is the development of neutralizing anti-adenoviral antibodies Encapsulation of recombinant adenovirus vectors in poly(lactic/glycolic acid) (PLGA) copolymer enables infection in vitro, in the presence of neutralizing antibodies and results in-the release of viable virus for over 100 h. Importantly, encapsulated adenovirus also shows diminished immunogenicity invivo. Mice immunized with encapsulated recombinant adenoviral vectors show a greater than 45-fold reduction in anti-adenovirus titers relative to non-encapsulated vectors. An extended release formulation of adenovirus that reduces viral immunogenicity and sequesters the viral particle form antibody exposure may improve in vivo efficacy.