Adeno-associated virus type 6 is retrogradely transported in the non-human primate brain
Open accessAbstract
We recently demonstrated that axonal transport of adeno-associated virus (AAV) is serotype-dependent. Thus, AAV serotype 2 (AAV2) is anterogradely transported (e.g., from cell bodies to nerve terminals) in both rat and non-human primate (NHP) brain. In contrast, AAV serotype 6 (AAV6) is retrogradely transported from terminals to neuronal cell bodies in the rat brain. However, the directionality of axonal transport of AAV6 in the NHP brain has not been determined. In this study, two Cynomolgus macaques received an infusion of AAV6 harboring green fluorescent protein (GFP) into the striatum (caudate and putamen) by magnetic resonance (MR)-guided convection-enhanced delivery. One month after infusion, immunohistochemical staining of brain sections revealed a striatal GFP expression that corresponded well with MR signal observed during gene delivery. As shown previously in rats, GFP expression was detected throughout the prefrontal, frontal and parietal cortex, as well as the substantia nigra pars compacta and thalamus, indicating retrograde transport of the vector in NHP. AAV6-GFP preferentially transduced neurons, although a few astrocytes were also transduced. Transduction of non-neuronal cells in the brain was associated with the upregulation of the major histocompatibility complex-II and lymphocytic infiltration as previously observed with AAV1 and AAV9. This contrasts with highly specific neuronal transduction in the rat brain. Retrograde axonal transport of AAV6 from a single striatal infusion permits efficient transduction of cortical neurons in significant tissue volumes that otherwise would be difficult to achieve.
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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 [14]
The Introduction (page unavailable) says AAV2 and AAV6 both show strongly neuronal tropism, supporting similarity between those two serotypes. But the Discussion (page unavailable) says AAV9 efficiently transduces astrocytes as well as neurons, unlike predominantly neuronal AAV6; the paper does not establish that differences are generally few when a constitutive promoter is used. (LLM, conf=0.84)
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 [14]
The Results (AAV6 tropism in NHP brain; page unavailable) show that AAV6 mainly transduced neurons after direct brain infusion, and the Discussion says the same has been demonstrated for AAV2. The paper does not establish this pattern for almost all known serotypes; the Discussion instead notes that AAV9 efficiently transduces both neurons and astrocytes. (LLM, conf=0.87)
Experimental — accuracy not yet measuredNo 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 [14]
The Results (‘AAV6 tropism in NHP brain’; page unavailable) report that most GFP-expressing cells after AAV6 infusion were neurons, supporting neuronal rather than primary oligodendrocyte tropism for AAV6 in this setting. The paper does not establish the claim about all AAV capsids in the literature or specify the constitutive-promoter condition. (LLM, conf=0.77)
Experimental — accuracy not yet measuredThe 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 [14]
The Introduction and Discussion describe AAV2 and AAV6 as strongly or mainly neuron-tropic, and the Results support this for AAV6 in non-human primate brain. But the Discussion says AAV9 efficiently transduces both neurons and astrocytes; the paper also notes non-neuronal transduction with AAV1 and provides no comparable tropism finding for AAV5 or AAV8. It therefore does not support the claim for the listed serotypes as a group. Page numbers were not supplied in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
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- Authors
- San Sebastian, W., Samaranch, L., Heller, G., Kells, A. P., Bringas, J., Pivirotto, P., Forsayeth, J., & Bankiewicz, K. S.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Bankiewicz, K S
- Venue
- Gene Therapy
- Published
- 2013-09-26
- Volume
- 20
- Issue
- 12
- Pages
- 1178-1183
- ISSN
- 0969-7128 (ISSN-L)
- 1476-5462
- PMC
- PMC3855617
- OpenAlex
- W1989743136
- Cited by
- 62
- References
- 23
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 5 · 2017: 6 · 2016: 11 · 2015: 4 · 2014: 4
- FWCI
- 4.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- University of California, San Francisco
- National Institute of Neurological Disorders and Stroke (R01NS073940)
- 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
- retrograde axonal transport, non-human primate brain, striatum, caudate and putamen, neuronal transduction, MHC class II upregulation, lymphocyte infiltration, gene delivery, macaque
- MeSH terms
- Dependovirus, Animals, Astrocytes, Axons, Axonal Transport, Brain, Caudate Nucleus, Female, Genetic Vectors, Macaca fascicularis, Magnetic Resonance Imaging, Neurons, Putamen, Transduction, Genetic, Green Fluorescent Proteins, Rats, Viral Tropism
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