THE IMMUNOSUPPRESSANT FK506 PROLONGS TRANSGENE EXPRESSION IN BRAIN FOLLOWING ADENOVIRUS-MEDIATED GENE-TRANSFER

FIRST generation, replication-defective adenoviral vectors are highly effective for gene transfer into the central nervous system, but the h ost's immune response limits the utility of this vector for possible t herapy of neurological disease or long-term gene transfer studies in e xperimental animals. We have demonstrated the effectiveness of FK506 ( tacrolimus), a powerful immunosuppressant that readily crosses the blo od-brain barrier, in maintaining adenovirus-mediated reporter gene tra nsfer following stereotaxic injection of the recombinant (AdCMVlacZ) i nto mouse striatum. After 28 days, beta-galactosidase expression was r educed by 75% relative to day 10 in immunocompetent animals, accompani ed by an inflammatory reaction in the region of transduced cells; howe ver, in mice receiving daily s.c. injections of FK506, beta-galactosid ase activity was maintained at the 10 days post-injection level.