Characterization of Adenoviral Gene Expression in Spinal Cord after Remote Vector Delivery

Characterization of Adenoviral Gene Expression in Spinal Cord after Remote Vector Delivery AbstractOBJECTIVE:Recent work has established that the remote injection of attenuated adenoviral vectors may result in central nervous system (CNS) gene expression. These studies suggest that virus passes through peripheral nerves into the CNS. The present experiment attempts to characterize this phenomenon systematically.METHODS:Spinal cord cells staining for the reporter gene β-galactosidase were histologically quantified after microinjection of the viral vector Ad5RSVntLacZ into rat footpad, muscle, or sciatic nerve. The effects of injection location, titer, and time, as well as nerve crush and dexamethasone, were examined.RESULTS:Sciatic nerve viral vector injection results in significantly higher CNS uptake than intramuscular and subcutaneous injections (P < 0.05). Nerve crush injury caused a time-dependent reduction in spinal cord gene uptake after sciatic nerve adenoviral injection (P < 0.05). Neuronal staining reaches its peak at 6 days after injection (P < 0.002). Peripheral nerve delivery 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 method for spinal cord gene therapy that avoids any manipulation of CNS tissue http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurosurgery Oxford University Press

Characterization of Adenoviral Gene Expression in Spinal Cord after Remote Vector Delivery

Characterization of Adenoviral Gene Expression in Spinal Cord after Remote Vector Delivery

Characterization of Adenoviral Gene Expression in Spinal Cord after Remote Vector Delivery Nicholas M. Boulis, M.D., Danielle E. Turner, Jessica A. Dice, B.S., Vikas Bhatia, B.S., Eva L. Feldman, M.D., Ph.D. Section of Neurosurgery (N M B, VB), Department of Neurology (DET, JAD, ELF), University of Michigan, Ann Arbor, Michigan OBJECTIVES: Recent work has established that the remote injection of attenuated adenoviral vectors may result in central nervous system (CNS) gene expression. These studies suggest that virus passes through peripheral nerves into the CNS. The present experiment attempts to characterize this phenomenon systematically. METHODS: Spinal cord cells staining for the reporter gene /3-galactosidase were histologically quantified after microinjection of the viral vector Ad5RSVntLacZ into rat footpad, muscle, or sciatic nerve. The effects of injection location, titer, and time, as well as nerve crush and dexamethasone, were examined. RESULTS: Sciatic nerve viral vector injection results in significantly higher CNS uptake than intramuscular and subcutaneous injections (P < 0.05). Nerve crush injury caused a time-dependent reduction in spinal cord gene uptake after sciatic nerve adenoviral injection (P < 0.05). Neuronal staining reaches its peak at 6 days after injection (P < 0.002). Peripheral nerve delivery 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 method for spinal cord gene therapy that avoids any manipulation of CNS tissue. (N eurosurgery 45:131-138, 1999) Keywords: Adenovirus, /3-Galactosidase, Gene therapy, Sciatic nerve, Spinal cord Viral gene delivery directly into central nervous system elivery of therapeutic compounds for treatment of tissue has the potential to solve this problem by inducing spinal cord dysfunction remains a challenge. The rec­...
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Publisher
Congress of Neurological Surgeons
Copyright
© Published by Oxford University Press.
ISSN
0148-396X
eISSN
1524-4040
D.O.I.
10.1097/00006123-199907000-00029
Publisher site
See Article on Publisher Site

Abstract

AbstractOBJECTIVE:Recent work has established that the remote injection of attenuated adenoviral vectors may result in central nervous system (CNS) gene expression. These studies suggest that virus passes through peripheral nerves into the CNS. The present experiment attempts to characterize this phenomenon systematically.METHODS:Spinal cord cells staining for the reporter gene β-galactosidase were histologically quantified after microinjection of the viral vector Ad5RSVntLacZ into rat footpad, muscle, or sciatic nerve. The effects of injection location, titer, and time, as well as nerve crush and dexamethasone, were examined.RESULTS:Sciatic nerve viral vector injection results in significantly higher CNS uptake than intramuscular and subcutaneous injections (P < 0.05). Nerve crush injury caused a time-dependent reduction in spinal cord gene uptake after sciatic nerve adenoviral injection (P < 0.05). Neuronal staining reaches its peak at 6 days after injection (P < 0.002). Peripheral nerve delivery 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 method for spinal cord gene therapy that avoids any manipulation of CNS tissue

Journal

NeurosurgeryOxford University Press

Published: Jul 1, 1999

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