title: Strong cortical and spinal cord transduction after AAV7 and AAV9 delivery into the cerebrospinal fluid of nonhuman primates.
abstract: The present study builds on previous work showing that infusion of adeno-associated virus type 9 (AAV9) into the cisterna magna (CM) of nonhuman primates resulted in widespread transduction throughout cortex and spinal cord. Transduction efficiency was severely limited, however, by the presence of circulating anti-AAV antibodies. Accordingly, we compared AAV9 to a related serotype, AAV7, which has a high capsid homology. CM infusion of either AAV7 or AAV9 directed high level of cell transduction with similar patterns of distribution throughout brain cortex and along the spinal cord. Dorsal root ganglia and corticospinal tracts were also transduced. Both astrocytes and neurons were transduced. Interestingly, little transduction was observed in peripheral organs. Our results indicate that intrathecal delivery of either AAV7 or AAV9 directs a robust and widespread cellular transduction in the central nervous system and other peripheral neural structures.
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, CA 94103, USA.
authors.forename: Lluis
authors.initials: L
authors.lastname: Samaranch
authors.forename: Ernesto A
authors.initials: EA
authors.lastname: Salegio
authors.forename: Waldy
authors.initials: W
authors.lastname: San Sebastian
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Kells
authors.forename: John R
authors.initials: JR
authors.lastname: Bringas
authors.forename: John
authors.initials: J
authors.lastname: Forsayeth
authors.forename: Krystof S
authors.initials: KS
authors.lastname: Bankiewicz
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000821:virology; D002540:Cerebral Cortex / Q000473:pathology / Q000821:virology; D000229:Dependovirus / Q000235:genetics*; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology / Q000821:virology; D018014:Gene Transfer Techniques / Q000009:adverse effects*; D005822:Genetic Vectors / Q000009:adverse effects* / Q000134:cerebrospinal fluid; D049452:Green Fluorescent Proteins / Q000235:genetics; D008251:Macaca / Q000235:genetics* / Q000821:virology; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology / Q000821:virology; D013116:Spinal Cord / Q000473:pathology / Q000821:virology; D014161:Transduction, Genetic
chemical_list: D049452:Green Fluorescent Proteins