Differential Transduction Following Basal Ganglia Administration of Distinct Pseudotyped AAV Capsid Serotypes in Nonhuman Primates
Open accessAbstract
We examined the transduction efficiency of different adeno-associated virus (AAV) capsid serotypes encoding for green fluorescent protein (GFP) flanked by AAV2 inverted terminal repeats in the nonhuman primate basal ganglia as a prelude to translational studies, as well as clinical trials in patients with Parkinson's disease (PD). Six intact young adult cynomolgus monkeys received a single 10 microl injection of AAV2/1-GFP, AAV2/5-GFP, or AAV2/8-GFP pseudotyped vectors into the caudate nucleus and putamen bilaterally in a pattern that resulted in each capsid serotype being injected into at least four striatal sites. GFP immunohistochemistry revealed excellent transduction rates for each AAV pseudotype. Stereological estimates of GFP+ cells within the striatum revealed that AAV2/5-GFP transduces significantly higher number of cells than AAV2/8-GFP (P < 0.05) and there was no significant difference between AAV2/5-GFP and AAV2/1-GFP (P = 0.348). Consistent with this result, Cavalieri estimates revealed that AAV2/5-GFP resulted in a significantly larger transduction volume than AAV2/8-GFP (P < 0.05). Each pseudotype transduced striatal neurons effectively [>95% GFP+ cells colocalized neuron-specific nuclear protein (NeuN)]. The current data suggest that AAV2/5 and AAV2/1 are superior to AAV2/8 for gene delivery to the nonhuman primate striatum and therefore better candidates for therapeutic applications targeting this structure.
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AAV capsid cell tropisms obtained in rodents are not always predictive of transduction specificity in primates.
“Moreover, the AAV capsid cell tropisms obtained in rodents are not always predictive of the transduction specificity in primates.”
From Novel oligodendroglial alpha synuclein viral vector models of multiple system atrophy: studies in rodents and nonhuman primates (2017) · cites this paper as [11]
The Discussion (page unavailable) says the primate results confirm earlier rodent findings on the tropism and transduction patterns of the serotypes studied. It does not address whether rodent capsid cell tropisms sometimes fail to predict transduction specificity in primates; agreement in this study does not rule out such failures elsewhere. (LLM, conf=0.73)
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References 49 · Cited by 86
- Authors
- Dodiya, H. B., Bjorklund, T., Stansell III, J., Mandel, R. J., Kirik, D., & Kordower, J. H.
- Affiliations
- Rush University Medical Center (US)
- University of Florida (US)
- Lund University (SE)
- Corresponding author
- Kordower, Jeffrey H
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 18
- Issue
- 3
- Pages
- 579-587
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC2839447
- OpenAlex
- W2045736514
- Cited by
- 86
- References
- 49
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 6 · 2018: 3 · 2017: 6 · 2016: 8 · 2015: 5 · 2014: 7 · 2013: 7 · 2012: 9
- FWCI
- 5.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS055143, NS055143)
- 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, AAV2/5, AAV2/8, gene delivery, basal ganglia, striatum, caudate nucleus, putamen, transduction efficiency, Parkinson's disease, non-human primates, Macaca fascicularis, stereology, green fluorescent protein
- MeSH terms
- Dependovirus, Animals, Basal Ganglia, Capsid, Genetic Techniques, Genetic Vectors, Macaca fascicularis, Male, Neurons, Parkinson Disease, Plasmids, Primates, Genetic Therapy, Microscopy, Confocal, Green Fluorescent Proteins
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