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 limitati on to its use in vivo is an inability lo redose to the brain.We show t hat one factor inhibiting re-dosing is the development of neutralizing anti-adenoviral antibodies Encapsulation oi recombinant adenovirus ve ctors in poly(lactic/glycolic acid) (PLGA) copolymer enables infection in vitro, in the presence of neutralizing antibodies and results in-t he release of viable virus for over 100 h. Importantly, encapsulated a denovirus also shows diminished immunogenicity invivo. Mice immunized with encapsulated recombinant adenoviral vectors show a greater than 4 5-fold reduction in anti-adenovirus titers relative to non-encapsulate d vectors. An extended release formulation of adenovirus that reduces viral immunogenicity and sequesters the viral particle form antibody e xposure may improve in vivo efficacy.