Characterization of adenoviral gene expression in spinal cord after remotevector delivery

OBJECTIVES: Recent work has established that the remote injection of attenu ated adenoviral vectors may result in central nervous system (CNS) gene exp ression. These studies suggest that virus passes through peripheral nerves into the CNS. The present experiment attempts to characterize this phenomen on systematically. METHODS: Spinal cord cells staining for the reporter gene beta-galactosidas e were histologically quantified after microinjection of the viral vector A d5RSVntLacZ into rat footpad, muscle, or sciatic nerve. The effects of inje ction location, titer, and time, as well as nerve crush and dexamethasone, were examined. RESULTS: Sciatic nerve viral vector injection results in significantly high er CNS uptake than intramuscular and subcutaneous injections (P < 0.05). Ne rve crush injury caused a time-dependent reduction in spinal cord gene upta ke after sciatic nerve adenoviral injection (P <: 0.05). Neuronal staining reaches its peak at 6 days after injection (P < 0.002). peripheral nerve de livery to the CNS increases with augmented titers (P < 0.03). Finally, gene expression is augmented by administration of dexamethasone (P < 0.0001). CONCLUSION: Remote adenoviral vector injection represents a potential metho d for spinal cord gene therapy that avoids any manipulation of CNS tissue.