Tropism and toxicity of adeno-associated viral vector serotypes 1, 2, 5, 6, 7, 8, and 9 in rat neurons and glia in vitro
Open accessAbstract
Recombinant adeno-associated viral (rAAV) vectors are frequently used for gene delivery to the central nervous system and are capable of transducing neurons and glia in vitro. In this study, seven serotypes of a rAAV vector expressing green fluorescent protein (GFP) were characterized for tropism and toxicity in primary cortical cells derived from embryonic rat brain. At 2 days after transduction, serotypes 1 and 5 through 8 expressed GFP predominately in glia, but by 6 days post-transduction expression was neuronal except for AAV5. AAV2 and 9 produced minimal GFP expression. Using cell viability assays, toxicity was observed at higher multiplicities of infection (MOI) for all serotypes except AAV2 and 9. The toxicity of AAV1 and 5-8 affected mostly glia as indicated by a loss of glial-marker immunoreactivity. A frameshift mutation in the GFP gene reduced overall toxicity for serotypes 1, 5 and 6, but not 7 and 8 suggesting that the toxicity was not solely due to the overexpression of GFP. Collectively, a differential tropism and toxicity was observed among the AAV serotypes on primary cortical cultures with an overall preferential glial transduction and toxicity.
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AAV has limitations in some gene therapy studies, such as toxicity and unnecessary immunoreaction, especially in neuroscience research.
“AAV also has been shown to have limitations in a few gene therapy studies, such as its toxicity and unnecessary immunoreaction, especially in neuroscience research [66,67].”
From Non-Integrating Lentiviral Vectors in Clinical Applications: A Glance Through (2022) · cites this paper as [66]
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Non-Integrating Lentiviral Vectors in Clinical Applications: A Glance Through
Gurumoorthy, N., Nordin, F., Tye, G. J., Wan Kamarul Zaman, W. S., & Ng, M. H. (2022) · Biomedicines · doi:10.3390/biomedicines10010107 · Cited by 69 · see citing works
- Authors
- Howard, D. B., Powers, K., Wang, Y., & Harvey, B. K.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Harvey, Brandon K.
- Venue
- Virology
- Publisher
- Elsevier BV
- Published
- 2008-03
- Volume
- 372
- Issue
- 1
- Pages
- 24-34
- ISSN
- 0042-6822 (ISSN-L)
- PMC
- PMC2293646
- OpenAlex
- W1985419351
- Cited by
- 149
- References
- 6
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 8 · 2023: 2 · 2022: 11 · 2021: 8 · 2020: 7 · 2019: 7 · 2018: 9 · 2017: 12 · 2016: 5 · 2015: 10 · 2014: 11 · 2013: 8 · 2012: 10
- FWCI
- 3.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Virology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health and Human Services
- National Institutes of Health (Z99 DA999999)
- National Institute on Drug Abuse
- 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, recombinant AAV vectors, viral tropism, neurotoxicity, neuronal transduction, GFP expression, frameshift mutation, central nervous system gene delivery, AAV1, AAV5, AAV6, AAV8, AAV9
- MeSH terms
- Dependovirus, Animals, Cells, Cultured, Cerebral Cortex, Female, Genetic Vectors, Neuroglia, Neurons, Phylogeny, Pregnancy, Serotyping, Transduction, Genetic, Rats, Sprague-Dawley, Gene Transfer Techniques, Green Fluorescent Proteins, Rats
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