Systemic AAVrh10 provides higher transgene expression than AAV9 in the brain and the spinal cord of neonatal mice
Open accessAbstract
Systemic delivery of self-complementary (sc) adeno-associated-virus vector of serotype 9 (AAV9) was recently shown to provide robust and widespread gene transfer to the central nervous system (CNS), opening new avenues for practical, and non-invasive gene therapy of neurological diseases. More recently, AAV of serotype rh10 (AAVrh10) was also found highly efficient to mediate CNS transduction after intravenous administration in mice. However, only a few studies compared AAV9 and AAVrh10 efficiencies, particularly in the spinal cord. In this study, we compared the transduction capabilities of AAV9 and AAVrh10 in the brain, the spinal cord, and the peripheral nervous system (PNS) after intravenous delivery in neonatal mice. As reported in previous studies, AAVrh10 achieved either similar or higher transduction than AAV9 in all the examined brain regions. The superiority of AAVrh10 over AAV9 appeared statistically significant only in the medulla and the cerebellum, but a clear trend was also observed in other structures like the hippocampus or the cortex. In contrast to previous studies, we found that AAVrh10 was more efficient than AAV9 for transduction of the dorsal spinal cord and the lower motor neurons (MNs). However, differences between the two serotypes appeared mainly significant at low dose, and surprisingly, increasing the dose did not improve AAVrh10 distribution in the spinal cord, in contrary to AAV9. Similar dose-related differences between transduction efficiency of the two serotypes were also observed in the sciatic nerve. These findings suggest differences in the transduction mechanisms of these two serotypes, which both hold great promise for gene therapy of neurological diseases.
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AAVrh.8 better transduces neurons, astrocytes, and oligodendrocytes and has low peripheral tropism compared to AAV9 and AAVrh.10.
“AAVrh.8 was shown to better transduce neurons, astrocytes, and oligodendrocytes, while with low peripheral tropism compared to AAV9 and AAVrh.10 [126, 127].”
From Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside (2024) · cites this paper as [126]
The Materials and methods section describes vectors of serotypes AAV9 and AAVrh10, not AAVrh.8. The Results compare those two serotypes in the peripheral nervous system and in the heart and liver, but provide no AAVrh.8 comparison. A search for AAVrh.8/AAVrh8 found no passage addressing its cell transduction or peripheral tropism. (LLM, conf=0.77)
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- Authors
- Tanguy, Y., Biferi, M. G., Besse, A., Astord, S., Cohen-Tannoudji, M., Marais, T., & Barkats, M.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Tanguy, Yannick
- Barkats, Martine
- Venue
- Frontiers in Molecular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2015-07-28
- Volume
- 8
- Pages
- 36-36
- ISSN
- 1662-5099 (ISSN-L)
- PMC
- PMC4516891
- OpenAlex
- W1548947111
- Cited by
- 103
- References
- 49
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 17 · 2023: 10 · 2022: 11 · 2021: 11 · 2020: 8 · 2019: 8 · 2018: 5 · 2017: 12 · 2016: 3
- FWCI
- 4.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Molecular Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique
- 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
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Keywords
- AAVrh10, AAV9, adeno-associated virus vectors, serotype comparison, intravenous gene delivery, spinal cord, brain, peripheral nervous system, sciatic nerve, lower motor neurons, dose dependence, transgene expression, neonatal mice
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