title: Comparative analyses of adeno-associated viral vector serotypes 1, 2, 5, 8 and 9 in marmoset, mouse and macaque cerebral cortex.
abstract: Here we investigated the transduction characteristics of adeno-associated viral vector (AAV) serotypes 1, 2, 5, 8 and 9 in the marmoset cerebral cortex. Using three constructs that each has hrGFP under ubiquitous (CMV), or neuron-specific (CaMKII and Synapsin I (SynI)) promoters, we investigated (1) the extent of viral spread, (2) cell type tropism, and (3) neuronal transduction efficiency of each serotype. AAV2 was clearly distinct from other serotypes in small spreading and neuronal tropism. We did not observe significant differences in viral spread among other serotypes. Regarding the cell tropism, AAV1, 5, 8 and 9 exhibited mostly glial expression for CMV construct. However, when the CaMKII construct was tested, cortical neurons were efficiently transduced (>∼70% in layer 3) by all serotypes, suggesting that glial expression obscured neuronal expression for CMV construct. For both SynI and CaMKII constructs, we observed generally high-level expression in large pyramidal cells especially in layer 5, as well as in parvalbumin-positive interneurons. The expression from the CaMKII construct was more uniformly observed in excitatory cells compared with SynI construct. Injection of the same viral preparations in mouse and macaque cortex resulted in essentially the same result with some species-specific differences.
authors.affiliation: Division of Brain Biology, National Institute for Basic Biology, Okazaki, Japan; Graduate University for Advanced Studies (SOKENDAI), Okazaki, Japan. Electronic address: watakabe@nibb.ac.jp.
authors.forename: Akiya
authors.initials: A
authors.lastname: Watakabe
authors.affiliation: Division of Brain Biology, National Institute for Basic Biology, Okazaki, Japan.
authors.forename: Masanari
authors.initials: M
authors.lastname: Ohtsuka
authors.affiliation: Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kinoshita
authors.affiliation: Division of Brain Biology, National Institute for Basic Biology, Okazaki, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takaji
authors.affiliation: Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Isa
authors.affiliation: Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mizukami
authors.affiliation: Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Japan.
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
authors.affiliation: Graduate University for Advanced Studies (SOKENDAI), Okazaki, Japan; Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Isa
authors.affiliation: Division of Brain Biology, National Institute for Basic Biology, Okazaki, Japan; Graduate University for Advanced Studies (SOKENDAI), Okazaki, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yamamori
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D002144:Callithrix; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008251:Macaca; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013045:Species Specificity; D016704:Synapsins / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D016704:Synapsins; D049452:Green Fluorescent Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: Monkey; Neuron; Non-human primate; Tropism; Viral vector; rAAV