Genomic integration and gene expression by a modified adenoviral vector

A replication-deficient recombinant adenovirus encoding luciferase was cons tructed using 5' and 3' long terminal repeat (LTR) sequences of the Moloney murine leukemia virus, Gene expression was observed in cultured cells in v itro and in submandibular gland, cortex, and caudate nucleus for as long as three months in vivo. The vector integrated randomly into the genome of bo th dividing and nondividing cells as determined by fluorescence in situ hyb ridization (FISH) (10-15% of cells in vitro and 5% in rat spleen in vivo), gene walking, Southern hybridization, and polymerase chain reaction (PCR), in the absence of transcomplementing reverse transcriptase or integrase act ivity. The new vector combines the high titer and versatility of adenoviral vectors with the long-term gene expression and integration of retroviral v ectors.