Cited by 283Virus-based gene therapy researchRNA Interference and Gene DeliveryExtracellular vesicles in disease

Microvesicle-associated AAV Vector as a Novel Gene Delivery System

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Maguire, Casey A, Balaj, Leonora, Sivaraman, Sarada, Crommentuijn, Matheus HW, Ericsson, Maria, Mincheva-Nilsson, Lucia, Baranov, Vladimir, Gianni, Davide +4 more·2012·Molecular Therapy

Abstract

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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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
Venue
Molecular Therapy
Publisher
Elsevier BV
Published
2012-05
Volume
20
Issue
5
Pages
960-971
ISSN
1525-0016 (ISSN-L)
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
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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