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Robust spinal motor neuron transduction following intrathecal delivery of AAV9 in pigs

Adeno-associated viral vector 9 (AAV9) has recently been shown to penetrate the blood-brain barrier via intravascular administration, making it a good candidate for diffuse gene delivery. However, the potential side effects of systemic delivery are unknown. Intrathecal viral vector administration may be more invasive than intravenous injections, but it requires far less vector and it can be performed on an outpatient basis, making it an ideal route of delivery for clinical translation. A total of 12 domestic farm pigs (<20 kg) underwent a single-level lumbar laminectomy with intrathecal catheter placement for AAV9 delivery. Animals were perfused and the tissue was harvested 30 days after treatment. Gene expression was assessed by anti-green fluorescent protein immunohistochemistry. Although a single lumbar injection resulted in gene expression limited to the lumbar segment of the spinal cord, three consecutive boluses via a temporary catheter resulted in diffuse transduction of motor neurons (MNs) throughout the cervical, thoracic and lumbar spinal cords. We now present the first successful robust transduction of MNs in the spinal cord of a large animal via intrathecal gene delivery using a self-complementary AAV9. These promising results can be translated to many MN diseases requiring diffuse gene delivery

Keywords : Animals,Blood-Brain Barrier,cytology,Dependovirus,Gene Expression,Gene Transfer Techniques,Genetic Vectors,genetics,Immunohistochemistry,Injections,Laminectomy,metabolism,Motor Neurons,Neurons,Neurosurgery,Spinal Cord,Swine,Transduction,Genetic,Universities,, Spinal,Motor,Neuron,Transduction,Following, injury claims london

Date of Publication : 2012 Aug

Authors : Federici T;Taub JS;Baum GR;Gray SJ;Grieger JC;Matthews KA;Handy CR;Passini MA;Samulski RJ;Boulis NM;

Organisation : Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322, USA

Journal of Publication : Gene Ther

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/21918551

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