title: Transduction Profile of the Marmoset Central Nervous System Using Adeno-Associated Virus Serotype 9 Vectors.
abstract: The common marmoset is a small New World primate that has attracted remarkable attention as a potential experimental animal link between rodents and humans. Adeno-associated virus (AAV) vector-mediated expression of a disease-causing gene or a potential therapeutic gene in the brain may allow the construction of a marmoset model of a brain disorder or an exploration of the possibility of gene therapy. To gain more insights into AAV vector-mediated transduction profiles in the marmoset central nervous system (CNS), we delivered AAV serotype 9 (AAV9) vectors expressing GFP to the cisterna magna or the cerebellar cortex. Intracisternally injected AAV9 vectors expanded in the CNS according to the cerebrospinal fluid (CSF) flow, by retrograde transport through neuronal axons or via intermediary transcytosis, resulting in diffuse and global transduction within the CNS. In contrast, cerebellar parenchymal injection intensely transduced a more limited area, including the cerebellar cortex and cerebellar afferents, such as neurons of the pontine nuclei, vestibular nucleus and inferior olivary nucleus. In the spinal cord, both administration routes resulted in labeling of the dorsal column and spinocerebellar tracts, presumably by retrograde transport from the medulla oblongata and cerebellum, respectively. Motor neurons and dorsal root ganglia were also transduced, possibly by diffusion of the vector down the subarachnoid space along the cord. Thus, these two administration routes led to distinct transduction patterns in the marmoset CNS, which could be utilized to generate different disease animal models and to deliver therapeutic genes for the treatment of diseases affecting distinct brain areas.
authors.affiliation: Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Matsuzaki
authors.affiliation: Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Konno
authors.affiliation: Department of Ophthalmology, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Mukai
authors.affiliation: Department of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Honda
authors.affiliation: Department of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Hirato
authors.affiliation: Department of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Yoshimoto
authors.affiliation: Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan. hirai@gunma-u.ac.jp.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hirai
mesh_terms: D000818:Animals; D002144:Callithrix; D002490:Central Nervous System / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D002531:Cerebellum / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D002946:Cisterna Magna / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D000229:Dependovirus / Q000235:genetics; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D017919:Hepatitis B Virus, Woodchuck; D008297:Male; D008392:Marmota; D051381:Rats; D014161:Transduction, Genetic / Q000379:methods*
keywords: Adeno-associated virus serotype 9 vector; Cerebellum; Common marmoset; Gene transfer; Spinal cord; Stereology