SYSTEMIC GENE-THERAPY - BIODISTRIBUTION AND LONG-TERM EXPRESSION OF ATRANSGENE IN MICE

We have investigated the in vivo efficacy of a systemic gene transfer method, which combines a liposomal delivery system (DLS liposomes) wit h episomally replicative DNA plasmids to effect long-term expression o f a transgene in cells, A single i,v, injection of a plasmid DNA vecto r containing the luciferase gene as a marker was administered with the DLS liposomes in BALB/c mice. The luciferase gene and its product wer e found in all mouse tissues tested as determined by PCR analysis and immunohistochemistry. Luciferase activity was also detected in all tis sues tested and was present in lung, liver, spleen, and heart up to 3 months postinjection, In contrast to the nonepisomal vectors tested (p RSV-luc and pCMVintlux), human papovavirus (BKV)-derived episomal vect ors showed long-term transgene expression, We found that these episoma l vectors replicated extrachromosomally in lung 2 weeks postinjection, Results indicated that transgene expression in specific tissues depen ded on the promoter element used, DNA/liposome formulation, dose of DN A per injection, and route of administration.