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Title

mRNA Delivery System for Targeting Antigen-Presenting Cells In Vivo

AuthorsFornaguera, Cristina ; Guerra-Rebollo, Marta; Lázaro, Miguel Ángel; Castells-Sala, Cristina; Meca-Cortés, Óscar ; Ramos-Perez, Victor; Cascante, Anna; Rubio, Núria ; Blanco, Jerónimo ; Borrós, Salvador
KeywordsSpleen
Antigen-presenting cells transfection
Immunotherapy
mRNA encapsulation and delivery
Oligopeptide-modified poly-(β-aminoester) polyplexes
Issue Date5-Sep-2018
PublisherWiley-Blackwell
CitationAdvanced Healthcare Materials 7 (17): 1800335 (2019)
AbstractThe encapsulation of mRNA in nanosystems as gene vaccines for immunotherapy purposes has experienced an exponential increase in recent years. Despite the many advantages envisaged within these approaches, their application in clinical treatments is still limited due to safety issues. These issues can be attributed, in part, to liver accumulation of most of the designed nanosystems and to the inability to transfect immune cells after an intravenous administration. In this context, this study takes advantage of the known versatile properties of the oligopeptide end-modified poly (β-amino esters) (OM-PBAEs) to complex mRNA and form discrete nanoparticles. Importantly, it is demonstrated that the selection of the appropriate end-oligopeptide modifications enables the specific targeting and major transfection of antigen-presenting cells (APC) in vivo, after intravenous administration, thus enabling their use for immunotherapy strategies. Therefore, with this study, it can be confirmed that OM-PBAE are appropriate systems for the design of mRNA-based immunotherapy approaches aimed to in vivo transfect APCs and trigger immune responses to fight either tumors or infectious diseases. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Publisher version (URL)https://doi.org/10.1002/adhm.201800335
URIhttp://hdl.handle.net/10261/202661
DOI10.1002/adhm.201800335
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