Comparative analyses of adeno-associated viral vector serotypes 1, 2, 5, 8 and 9 in marmoset, mouse and macaque cerebral cortex
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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.
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AAV9 and AAV.rh10 provided widespread expression patterns beyond the injection site with glia- and neuron-tropism respectively.
“On the contrary, AAV9 and AAV.rh10 provided widespread expression patterns beyond the injection site with glia- and neuron-tropism respectively [78, 79].”
From Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside (2024) · cites this paper as [78]
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- Authors
- Watakabe, A., Ohtsuka, M., Kinoshita, M., Takaji, M., Isa, K., Mizukami, H., Ozawa, K., Isa, T., & Yamamori, T.
- Affiliations
- National Institute for Basic Biology (JP)
- National Institute for Physiological Sciences (JP)
- Jichi Medical University (JP)
- The Graduate University for Advanced Studies, SOKENDAI (JP)
- Corresponding author
- Watakabe, Akiya
- ORCID
- Venue
- Neuroscience Research
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 93
- Pages
- 144-157
- ISSN
- 0168-0102 (ISSN-L)
- OpenAlex
- W1970839656
- Cited by
- 303
- References
- 4
- Citations by year
- 2026: 17 · 2025: 31 · 2024: 26 · 2023: 30 · 2022: 32 · 2021: 31 · 2020: 34 · 2019: 25 · 2018: 21 · 2017: 23 · 2016: 22 · 2015: 11
- FWCI
- 12.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuroscience Research (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (20240030, 22500300, 40290910)
- Ministry of Education, Culture, Sports, Science and Technology (22123009, 23123510)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- adeno-associated virus serotypes, AAV1, AAV2, AAV5, AAV8, AAV9, cerebral cortex, neuronal transduction, viral spread, CMV promoter, glial expression, parvalbumin interneurons, pyramidal neurons, layer 5, marmoset, mice, macaque, species differences
- MeSH terms
- Dependovirus, Animals, Callithrix, Cerebral Cortex, Female, Genetic Vectors, Macaca, Male, Mice, Inbred C57BL, Neurons, Promoter Regions, Genetic, Species Specificity, Transduction, Genetic, Synapsins, Green Fluorescent Proteins, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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