title: Adeno-associated virus serotypes 9 and rh10 mediate strong neuronal transduction of the dog brain.
abstract: Canine models have many advantages for evaluating therapy of human central nervous system (CNS) diseases. In contrast to nonhuman primate models, naturally occurring canine CNS diseases are common. In contrast to murine models, the dog's lifespan is long, its brain is large and the diseases affecting it commonly have the same molecular, pathological and clinical phenotype as the human diseases. We compared the ability of four intracerebrally injected adeno-associated virus vector (AAV) serotypes to transduce the dog brain with green fluorescent protein as the first step in using these vectors to evaluate both delivery and efficacy in naturally occurring canine homologs of human diseases. Quantitative measures of transduction, maximum diameter and area, identified both AAV2/9 and AAV2/rh10 as significantly more efficient than either AAV2/1 or AAV2/5 at transducing cerebral cortex, caudate nucleus, thalamus and internal capsule. Fluorescence co-labeling with cell-type-specific antibodies demonstrated that AAV2/9 and AAV2/rh10 were capable of primarily transducing neurons, although glial transduction was also identified and found to be more efficient with the AAV2/9 vector. These data are a prerequisite to evaluating the efficacy of recombinant AAV vectors carrying disease-modifying transgenes to treat naturally occurring canine models in preclinical studies of human CNS disease therapy.
authors.affiliation: Departments of Clinical Studies and Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: G P
authors.initials: GP
authors.lastname: Swain
authors.affiliation: Departments of Clinical Studies and Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Prociuk
authors.affiliation: Departments of Clinical Studies and Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Bagel
authors.affiliation: Departments of Clinical Studies and Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: P
authors.initials: P
authors.lastname: O'Donnell
authors.affiliation: Departments of Clinical Studies and Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Berger
authors.affiliation: Departments of Clinical Studies and Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Drobatz
authors.affiliation: Departments of Clinical Studies and Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Gurda
authors.affiliation: Departments of Clinical Studies and Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Haskins
authors.affiliation: Departments of Internal Medicine and Genetics, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Sands
authors.affiliation: Departments of Clinical Studies and Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Vite
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000821:virology; D002421:Caudate Nucleus / Q000378:metabolism / Q000821:virology; D002540:Cerebral Cortex / Q000378:metabolism / Q000821:virology; D000229:Dependovirus / Q000145:classification / Q000235:genetics* / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D020772:Internal Capsule / Q000378:metabolism / Q000821:virology; D012703:Serotyping; D013788:Thalamus / Q000378:metabolism / Q000821:virology; D014161:Transduction, Genetic; D019076:Transgenes
chemical_list: D049452:Green Fluorescent Proteins