Extracellular vesicles provide a capsid-free vector for oncolytic adenoviral DNA delivery

Heikki Saari; Tiia Turunen; Andres Lõhmus; Mikko Turunen; Matti Jalasvuori; Sarah J. Butcher; Seppo Ylä-Herttuala; Tapani Viitala; Vincenzo Cerullo; Pia R.M. Siljander; Marjo Yliperttula

doi:10.1080/20013078.2020.1747206

Extracellular vesicles provide a capsid-free vector for oncolytic adenoviral DNA delivery

Heikki Saari^*, Tiia Turunen, Andres Lõhmus, Mikko Turunen, Matti Jalasvuori, Sarah J. Butcher, Seppo Ylä-Herttuala, Tapani Viitala, Vincenzo Cerullo, Pia R.M. Siljander, Marjo Yliperttula

^*Corresponding author for this work

Research output: Contribution to journal › Article › Scientific › peer-review

47 Citations (Scopus)

Abstract

Extracellular vesicles (EVs) have been showcased as auspicious candidates for delivering therapeutic cargo, including oncolytic viruses for cancer treatment. Delivery of oncolytic viruses in EVs could provide considerable advantages, hiding the viruses from the immune system and providing alternative entry pathways into cancer cells. Here we describe the formation and viral cargo of EVs secreted by cancer cells infected with an oncolytic adenovirus (IEVs, infected cell-derived EVs) as a function of time after infection. IEVs were secreted already before the lytic release of virions and their structure resembled normally secreted EVs, suggesting that they were not just apoptotic fragments of infected cells. IEVs were able to carry the viral genome and induce infection in other cancer cells. As such, the role of EVs in the life cycle of adenoviruses may be an important part of a successful infection and may also be harnessed for cancer- and gene therapy.

Original language	English
Article number	1747206
Journal	Journal of extracellular vesicles
Volume	9
Issue number	1
DOIs	https://doi.org/10.1080/20013078.2020.1747206
Publication status	Published - 1 Jan 2020
Externally published	Yes
MoE publication type	A1 Journal article-refereed

Funding

We thank Benita Löflund, Pasi Laurinmäki (University of Helsinki), Instruct-FI, the Biocenter Finland National cryo-electron microscopy units, the Electron Microscopy Unit of the Institute of Biotechnology, the Instruct-HiLIFE Biocomplex unit, member of Biocenter Finland and Instruct-FI and the EV-core, for providing technical assistance and facilities to carry out the work. We would also like to thank the Academy of Finland, Alfred Kordelin foundation and Emil Aaltonen foundation for funding this project. This work was supported by the Academy of Finland [287089, 292275, 268376, 314985, 328601, 315409]; Alfred Kordelinin S??ti? [160385]; Emil Aaltosen S??ti? [170223]; Suomen Kulttuurirahasto [2018]. We thank Benita L?flund, Pasi Laurinm?ki (University of Helsinki), Instruct-FI, the Biocenter Finland National cryo-electron microscopy units, the Electron Microscopy Unit of the Institute of Biotechnology, the Instruct-HiLIFE Biocomplex unit, member of Biocenter Finland and Instruct-FI and the EV-core, for providing technical assistance and facilities to carry out the work. We would also like to thank the Academy of Finland, Alfred Kordelin foundation and Emil Aaltonen foundation for funding this project.

Keywords

adenovirus
cancer therapy
DNA delivery
Extracellular vesicles

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10.1080/20013078.2020.1747206

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@article{6ede6b5448374a3c995484d7951e0555,

title = "Extracellular vesicles provide a capsid-free vector for oncolytic adenoviral DNA delivery",

abstract = "Extracellular vesicles (EVs) have been showcased as auspicious candidates for delivering therapeutic cargo, including oncolytic viruses for cancer treatment. Delivery of oncolytic viruses in EVs could provide considerable advantages, hiding the viruses from the immune system and providing alternative entry pathways into cancer cells. Here we describe the formation and viral cargo of EVs secreted by cancer cells infected with an oncolytic adenovirus (IEVs, infected cell-derived EVs) as a function of time after infection. IEVs were secreted already before the lytic release of virions and their structure resembled normally secreted EVs, suggesting that they were not just apoptotic fragments of infected cells. IEVs were able to carry the viral genome and induce infection in other cancer cells. As such, the role of EVs in the life cycle of adenoviruses may be an important part of a successful infection and may also be harnessed for cancer- and gene therapy.",

keywords = "adenovirus, cancer therapy, DNA delivery, Extracellular vesicles",

author = "Heikki Saari and Tiia Turunen and Andres L{\~o}hmus and Mikko Turunen and Matti Jalasvuori and Butcher, \{Sarah J.\} and Seppo Yl{\"a}-Herttuala and Tapani Viitala and Vincenzo Cerullo and Siljander, \{Pia R.M.\} and Marjo Yliperttula",

note = "Funding Information: We thank Benita L{\"o}flund, Pasi Laurinm{\"a}ki (University of Helsinki), Instruct-FI, the Biocenter Finland National cryo-electron microscopy units, the Electron Microscopy Unit of the Institute of Biotechnology, the Instruct-HiLIFE Biocomplex unit, member of Biocenter Finland and Instruct-FI and the EV-core, for providing technical assistance and facilities to carry out the work. We would also like to thank the Academy of Finland, Alfred Kordelin foundation and Emil Aaltonen foundation for funding this project. Funding Information: This work was supported by the Academy of Finland [287089, 292275, 268376, 314985, 328601, 315409]; Alfred Kordelinin S??ti? [160385]; Emil Aaltosen S??ti? [170223]; Suomen Kulttuurirahasto [2018]. We thank Benita L?flund, Pasi Laurinm?ki (University of Helsinki), Instruct-FI, the Biocenter Finland National cryo-electron microscopy units, the Electron Microscopy Unit of the Institute of Biotechnology, the Instruct-HiLIFE Biocomplex unit, member of Biocenter Finland and Instruct-FI and the EV-core, for providing technical assistance and facilities to carry out the work. We would also like to thank the Academy of Finland, Alfred Kordelin foundation and Emil Aaltonen foundation for funding this project. Publisher Copyright: {\textcopyright} 2020, {\textcopyright} 2020 The Author(s). Published by Informa UK Limited, trading as Taylor \& Francis Group on behalf of The International Society for Extracellular Vesicles.",

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month = jan,

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doi = "10.1080/20013078.2020.1747206",

language = "English",

volume = "9",

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T1 - Extracellular vesicles provide a capsid-free vector for oncolytic adenoviral DNA delivery

AU - Saari, Heikki

AU - Turunen, Tiia

AU - Lõhmus, Andres

AU - Turunen, Mikko

AU - Jalasvuori, Matti

AU - Butcher, Sarah J.

AU - Ylä-Herttuala, Seppo

AU - Viitala, Tapani

AU - Cerullo, Vincenzo

AU - Siljander, Pia R.M.

AU - Yliperttula, Marjo

N1 - Funding Information: We thank Benita Löflund, Pasi Laurinmäki (University of Helsinki), Instruct-FI, the Biocenter Finland National cryo-electron microscopy units, the Electron Microscopy Unit of the Institute of Biotechnology, the Instruct-HiLIFE Biocomplex unit, member of Biocenter Finland and Instruct-FI and the EV-core, for providing technical assistance and facilities to carry out the work. We would also like to thank the Academy of Finland, Alfred Kordelin foundation and Emil Aaltonen foundation for funding this project. Funding Information: This work was supported by the Academy of Finland [287089, 292275, 268376, 314985, 328601, 315409]; Alfred Kordelinin S??ti? [160385]; Emil Aaltosen S??ti? [170223]; Suomen Kulttuurirahasto [2018]. We thank Benita L?flund, Pasi Laurinm?ki (University of Helsinki), Instruct-FI, the Biocenter Finland National cryo-electron microscopy units, the Electron Microscopy Unit of the Institute of Biotechnology, the Instruct-HiLIFE Biocomplex unit, member of Biocenter Finland and Instruct-FI and the EV-core, for providing technical assistance and facilities to carry out the work. We would also like to thank the Academy of Finland, Alfred Kordelin foundation and Emil Aaltonen foundation for funding this project. Publisher Copyright: © 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles.

PY - 2020/1/1

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N2 - Extracellular vesicles (EVs) have been showcased as auspicious candidates for delivering therapeutic cargo, including oncolytic viruses for cancer treatment. Delivery of oncolytic viruses in EVs could provide considerable advantages, hiding the viruses from the immune system and providing alternative entry pathways into cancer cells. Here we describe the formation and viral cargo of EVs secreted by cancer cells infected with an oncolytic adenovirus (IEVs, infected cell-derived EVs) as a function of time after infection. IEVs were secreted already before the lytic release of virions and their structure resembled normally secreted EVs, suggesting that they were not just apoptotic fragments of infected cells. IEVs were able to carry the viral genome and induce infection in other cancer cells. As such, the role of EVs in the life cycle of adenoviruses may be an important part of a successful infection and may also be harnessed for cancer- and gene therapy.

AB - Extracellular vesicles (EVs) have been showcased as auspicious candidates for delivering therapeutic cargo, including oncolytic viruses for cancer treatment. Delivery of oncolytic viruses in EVs could provide considerable advantages, hiding the viruses from the immune system and providing alternative entry pathways into cancer cells. Here we describe the formation and viral cargo of EVs secreted by cancer cells infected with an oncolytic adenovirus (IEVs, infected cell-derived EVs) as a function of time after infection. IEVs were secreted already before the lytic release of virions and their structure resembled normally secreted EVs, suggesting that they were not just apoptotic fragments of infected cells. IEVs were able to carry the viral genome and induce infection in other cancer cells. As such, the role of EVs in the life cycle of adenoviruses may be an important part of a successful infection and may also be harnessed for cancer- and gene therapy.

KW - adenovirus

KW - cancer therapy

KW - DNA delivery

KW - Extracellular vesicles

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DO - 10.1080/20013078.2020.1747206

M3 - Article

AN - SCOPUS:85083485596

SN - 2001-3078

VL - 9

JO - Journal of extracellular vesicles

JF - Journal of extracellular vesicles

IS - 1

M1 - 1747206

ER -

Extracellular vesicles provide a capsid-free vector for oncolytic adenoviral DNA delivery

Abstract

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Keywords

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