Microvesicle-associated AAV Vector as a Novel Gene Delivery System
Open accessAbstract
Adeno-associated virus (AAV) vectors have shown remarkable efficiency for gene delivery to cultured cells and in animal models of human disease. However, limitations to AAV vectored gene transfer exist after intravenous transfer, including off-target gene delivery (e.g., liver) and low transduction of target tissue. Here, we show that during production, a fraction of AAV vectors are associated with microvesicles/exosomes, termed vexosomes (vector-exosomes). AAV capsids associated with the surface and in the interior of microvesicles were visualized using electron microscopy. In cultured cells, vexosomes outperformed conventionally purified AAV vectors in transduction efficiency. We found that purified vexosomes were more resistant to a neutralizing anti-AAV antibody compared to conventionally purified AAV. Finally, we show that vexosomes bound to magnetic beads can be attracted to a magnetized area in cultured cells. Vexosomes represent a unique entity which offers a promising strategy to improve gene delivery.
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During AAV production, a fraction of AAV vectors are wrapped in microvesicles/exosomes.
“During AAV production, a fraction of AAV vectors were wrapped in microvesicles/exosomes, as observed using transmission electron micrograph [145]”
From Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside (2024) · cites this paper as [145]
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“It was recently shown that AAV vectors produced in cell culture can be detected within such exosomes and may be purified from the extracellular media (Maguire et al., 2012; Hudry et al., 2016).”
Background
- Authors
- Maguire, C. A., Balaj, L., Sivaraman, S., Crommentuijn, M. H., Ericsson, M., Mincheva-Nilsson, L., Baranov, V., Gianni, D., Tannous, B. A., Sena-Esteves, M., Breakefield, X. O., & Skog, J.
- Affiliations
- Harvard University (US)
- Umeå University (SE)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Skog, Johan
- ORCID
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 20
- Issue
- 5
- Pages
- 960-971
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC3345986
- OpenAlex
- W1994710975
- Cited by
- 283
- References
- 47
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 24 · 2023: 22 · 2022: 17 · 2021: 32 · 2020: 34 · 2019: 26 · 2018: 21 · 2017: 13 · 2016: 19 · 2015: 15 · 2014: 19 · 2013: 8 · 2012: 8
- FWCI
- 9.64
- 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)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Cancer Institute (P50-CA-86355, P01CA069246, R01CA141150, P50CA086355)
- National Institute of Neurological Disorders and Stroke (P30NS4577, P30NS045776)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- adeno-associated virus vectors, microvesicles, exosomes, gene delivery, transduction efficiency, magnetic bead separation, vector purification
- MeSH terms
- Dependovirus, Capsid, Centrifugation, Density Gradient, Genetic Vectors, Humans, Microscopy, Electron, Neoplasms, Transduction, Genetic, Transfection, Genetic Therapy, Gene Transfer Techniques, Cell Line, Tumor
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