PERSISTENCE IN MUSCLE OF AN ADENOVIRAL VECTOR THAT LACKS ALL VIRAL GENES

Genetic correction of inherited muscle diseases, such as Duchenne musc ular dystrophy, will require long term expression of the recombinant p rotein following gene transfer, We have shown previously that a new ad enoviral vector that lacks all viral genes expressed both full-length dystrophin and beta-gatactosidase in mdr (dystrophin-deficient) mouse muscle. We observed a significant histologic improvement of vector-tra nsduced mdx muscle before the eventual loss of vector-encoded transgen e expression, In this study, we investigated whether an immunological response against vector-encoded beta-galactosidase contributed to the loss of vector expression and affected vector persistence in muscle. I ntramuscular vector injection in control normal mice resulted in an ea rly and complete loss of beta-galactosidase expression accompanied by predominantly CD4(+) and CD8(+) lymphocytic infiltration and a signifi cant loss of vector DNA, In contrast, intramuscular vector injection i n lacZ transgenic mice resulted in persistent expression of beta-galac tosidase for at least 84 days with no evidence of inflammation or sign ificant loss of vector DNA, Our studies demonstrate that, in the absen ce of an immune response induced by beta-galactosidase expression, an adenoviral vector lacking all viral genes is stably maintained in musc le.