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Utilizing the Antigen Capsid-Incorporation Strategy for the Development of Adenovirus Serotype 5-Vectored Vaccine Approaches
Published on: May 6, 2015
Extracellular vesicles provide a capsid-free vector for oncolytic adenoviral DNA delivery
Heikki Saari1, Tiia Turunen2, Andres Lõhmus1
1Division of Pharmaceutical Biosciences and Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
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.
Insights
Extracellular vesicles (EVs) carrying oncolytic adenoviruses were secreted by infected cancer cells. These infected cell-derived EVs (IEVs) can infect other cancer cells, offering potential for cancer and gene therapy.
Area of Science:
- Oncology
- Virology
- Nanomedicine
Background:
- Extracellular vesicles (EVs) are explored for therapeutic delivery, including oncolytic viruses for cancer treatment.
- EVs may shield viruses from the immune system and facilitate cancer cell entry.
Purpose of the Study:
- To investigate the formation and viral cargo of EVs secreted by adenovirus-infected cancer cells over time.
- To assess the therapeutic potential of these infected cell-derived EVs (IEVs).
Main Methods:
- Cancer cells were infected with an oncolytic adenovirus.
- EVs secreted by infected cells (IEVs) were collected at different time points.
- IEVs were analyzed for viral genome content and infectivity in recipient cancer cells.
Main Results:
- IEVs were secreted before viral lysis and resembled normal EVs, not apoptotic fragments.
- IEVs successfully carried the adenovirus genome.
- IEVs induced infection in untreated cancer cells.
Conclusions:
- EVs play a role in the adenovirus life cycle.
- IEVs can be utilized for effective cancer and gene therapy delivery.
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