title: Trans-neuronal transduction of spinal neurons following cortical injection and anterograde axonal transport of a bicistronic AAV1 vector.
abstract: Adeno-associated viral (AAV) vectors are one of the most promising gene delivery systems to the central nervous system. We now report, that AAV1 can be used to express transgenes trans-neuronally in neurons distant from the injection site. Specifically, intracortical injection of a bicistronic AAV1 vector trans-neuronally transduced spinal neurons as shown by fluorescence microscopy, the presence of AAV genome and AAV transcript in the contralateral spinal cord. Prior pyramidotomy abolished spinal transduction, confirming anterograde axonal transport of AAV1 in the corticospinal tract. These observations demonstrate the potential of bicistronic AAV1 for trans-neuronal expression of therapeutic transgenes in neurological disorders or reporter genes in connectivity studies.
authors.affiliation: Centre for Restorative Neuroscience, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors.forename: T H
authors.initials: TH
authors.lastname: Hutson
authors.affiliation: Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Kathe
authors.affiliation: Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
authors.forename: L D F
authors.initials: LD
authors.lastname: Moon
mesh_terms: D000818:Animals; D001370:Axonal Transport; D000229:Dependovirus / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D066191:Sensorimotor Cortex / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D014161:Transduction, Genetic