Expanded Repertoire of AAV Vector Serotypes Mediate Unique Patterns of Transduction in Mouse Brain
Open accessAbstract
A wide diversity of adeno-associated virus (AAV) structural proteins uncovered from latent genomes in primate tissue has expanded the number of AAV vector serotypes, which can potentially confer unique cell tropism to the vector. We evaluated 17 of these vectors in the mouse brain using green fluorescent protein (GFP) as a reporter gene. A rapid initial evaluation was performed by neonatal lateral ventricle injections. Vectors made with capsids hu.32, hu.37, pi.2, hu.11, rh.8, hu.48R3, and AAV9 for comparison were selected for further analysis based on their ability to transduce large numbers of cells and result in novel patterns of cell transduction. These vectors were injected into adult brains in four major structures (cortex, striatum, hippocampus, and thalamus), and all were found to transduce neurons. In addition, hu.32, hu.11, pi.2, hu.48R3, and rh.8 resulted in GFP expression in some astrocytes or oligodendrocytes. AAVs rh.8, pi.2, hu.32, and hu.11 also appeared to result in neuronal transport of the vector genome. Vector transport was studied by a single unilateral injection into the hippocampus and vector genome was found in projection sites of the hippocampus. These unique patterns of cell transduction expand the potential repertoire for targeting AAV vectors to selected subsets of brain cells.
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Very few differences exist in the cellular tropism among AAV serotypes when a constitutive promoter drives gene expression.
“very few differences exist in the cellular tropism, when a constitutive promoter drives gene expression.”
From Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism (2016) · cites this paper as [13]
Materials and Methods (AAV vector construction and packaging; page unavailable) says all vectors used the same cytomegalovirus promoter. Under that condition, the Discussion (page unavailable) reports distinct transduction profiles and identifies capsids that expressed GFP in astrocytes where related serotypes did not. The paper therefore highlights differences in cellular tropism rather than saying there were very few. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredAAV8 and AAV9 exhibit a dominant neuronal tropism after direct injection into the rodent striatum as well as in other brain structures.
“AAV8 and AAV9 exhibit a dominant neuronal tropism after direct injection into the rodent striatum9,13,16,27 as well as in other brain structures.12,28,29”
From Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism (2016) · cites this paper as [13]
The Abstract (page not provided) reports that AAV9 was injected into the adult mouse striatum and other brain structures and transduced neurons; the Discussion says AAV vectors generally transduce neurons preferentially. But this paper did not test AAV8 by direct injection into those adult brain structures, so it does not establish the claimed striatal tropism for AAV8. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAfter direct CNS infusion, almost all of the known AAV serotypes exhibit a dominant neuronal tropism.
“after direct CNS infusion, almost all of the known AAV serotypes exhibit a dominant neuronal tropism”
From Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism (2016) · cites this paper as [13]
No AAV capsid has been described in the literature to exhibit a primary oligodendrocyte tropism when a constitutive promoter drives gene expression.
“No adeno-associated virus (AAV) capsid has been described in the literature to exhibit a primary oligodendrocyte tropism when a constitutive promoter drives gene expression”
From Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism (2016) · cites this paper as [13]
The vast majority of AAV vectors, such as AAV1, 2, 5, 6, 8 or 9, exhibit a dominant neuronal tropism in the central nervous system.
“The vast majority of AAV vectors, such as AAV1, 2, 5, 6, 8 or 9, exhibit a dominant neuronal tropism in the central nervous system.”
From Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism (2016) · cites this paper as [13]
Substantial neuronal tropism appears to be a central feature across widely diverse AAV capsid structures.
“Clearly, substantial neuronal tropism appears to be a central feature across widely diverse AAV capsid structures.”
From Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism (2016) · cites this paper as [13]
AAV1, AAV8, AAV9, and AAVrh.10 are primarily neurotropic in their transduction capacity.
“it has been shown that AAV1, AAV8, AAV9, and AAVrh.10 are primarily neurotropic in their transduction capacity”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [68]
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- Authors
- Cearley, C. N., Vandenberghe, L. H., Parente, M. K., Carnish, E. R., Wilson, J. M., & Wolfe, J. H.
- Affiliations
- University of Pennsylvania (US)
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Wolfe, John H
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 16
- Issue
- 10
- Pages
- 1710-1718
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC3056207
- OpenAlex
- W1993801613
- Cited by
- 182
- References
- 43
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 8 · 2023: 2 · 2022: 10 · 2021: 7 · 2020: 7 · 2019: 15 · 2018: 10 · 2017: 10 · 2016: 2 · 2015: 16 · 2014: 25 · 2013: 13 · 2012: 9
- FWCI
- 6.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DK47757, DK63690, NS38690, NS07180)
- 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 vectors, AAV serotypes, cell tropism, neuronal transduction, hippocampus, lateral ventricle injection, brain targeting, AAV9, Pi2
- MeSH terms
- Dependovirus, Animals, Brain, Genetic Vectors, Phylogeny, Transduction, Genetic, In Situ Hybridization, Green Fluorescent Proteins, Mice
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