mRNA Delivery System for Targeting Antigen-Presenting Cells In Vivo

The 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, WeinheimFinancial support from MINECO/FEDER (grants RTC-2015-3751-1, SAF2015-64927-C2-1-R and SAF2015-64927-C2-2-R) and Instituto de Salud Carlos III (Red Temática de Investigación Cooperativa en Terapia Celular-TERCEL) are acknowledged. CIBER-BBN is an initiative funded by the VI National R&D&I Plan2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. C.F. is grateful to MINECO for their Postdoctoral Fellowship (grant Torres Quevedo 2015). The Support of Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) from Generalitat de Catalunya for their support trough SGR 2014 1170 grant. Authors acknowledge the kind support of Marta Vives group on the digestion of spleens; Marco A. Fernández and Gerard Requena for the FACS measures and analysis and Irene Porcar and Elena García-Ollé for their kind support in experiments performance.Peer reviewe