The immunosuppressant FK506 prolongs transgene expression in brain following adenovirus-mediated gene transfer.

摘要: First generation, replication-defective adenoviral vectors are highly effective for gene transfer into the central nervous system, but host's immune response limits utility of this vector possible therapy neurological disease or long-term studies in experimental animals. We have demonstrated effectiveness FK506 (tacrolimus), a powerful immunosuppressant that readily crosses blood-brain barrier, maintaining adenovirus-mediated reporter following stereotaxic injection recombinant (AdCMVlacZ) mouse striatum. After 28 days, beta-galactosidase expression was reduced by 75% relative to day 10 immunocompetent animals, accompanied an inflammatory reaction region transduced cells; however, mice receiving daily s.c. injections FK506, activity maintained at days post-injection level.