Smuggling on the Nanoscale—Fusogenic Liposomes Enable Efficient RNA-Transfer with Negligible Immune Response In Vitro and In Vivo
Marco Hoffmann,
Sven Gerlach,
Masanari Takamiya,
Samar Tarazi,
Nils Hersch,
Agnes Csiszár,
Ronald Springer,
Georg Dreissen,
Hanno Scharr,
Sepand Rastegar,
Tanja Beil,
Uwe Strähle,
Rudolf Merkel,
Bernd Hoffmann
Affiliations
Marco Hoffmann
IBI-2: Mechanobiology, Institute of Biological Information Processing, Forschungszentrum Jülich, 52428 Jülich, Germany
Sven Gerlach
IBI-2: Mechanobiology, Institute of Biological Information Processing, Forschungszentrum Jülich, 52428 Jülich, Germany
Masanari Takamiya
Institute of Biological and Chemical Systems-Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, Germany
Samar Tarazi
IBI-2: Mechanobiology, Institute of Biological Information Processing, Forschungszentrum Jülich, 52428 Jülich, Germany
Nils Hersch
IBI-2: Mechanobiology, Institute of Biological Information Processing, Forschungszentrum Jülich, 52428 Jülich, Germany
Agnes Csiszár
IBI-2: Mechanobiology, Institute of Biological Information Processing, Forschungszentrum Jülich, 52428 Jülich, Germany
Ronald Springer
IBI-2: Mechanobiology, Institute of Biological Information Processing, Forschungszentrum Jülich, 52428 Jülich, Germany
Georg Dreissen
IBI-2: Mechanobiology, Institute of Biological Information Processing, Forschungszentrum Jülich, 52428 Jülich, Germany
Hanno Scharr
IAS-8: Data Analytics and Machine Learning, Institute for Advanced Simulation, Forschungszentrum Jülich, 52428 Jülich, Germany
Sepand Rastegar
Institute of Biological and Chemical Systems-Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, Germany
Tanja Beil
Institute of Biological and Chemical Systems-Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, Germany
Uwe Strähle
Institute of Biological and Chemical Systems-Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, Germany
Rudolf Merkel
IBI-2: Mechanobiology, Institute of Biological Information Processing, Forschungszentrum Jülich, 52428 Jülich, Germany
Bernd Hoffmann
IBI-2: Mechanobiology, Institute of Biological Information Processing, Forschungszentrum Jülich, 52428 Jülich, Germany
The efficient and biocompatible transfer of nucleic acids into mammalian cells for research applications or medical purposes is a long-standing, challenging task. Viral transduction is the most efficient transfer system, but often entails high safety levels for research and potential health impairments for patients in medical applications. Lipo- or polyplexes are commonly used transfer systems but result in comparably low transfer efficiencies. Moreover, inflammatory responses caused by cytotoxic side effects were reported for these transfer methods. Often accountable for these effects are various recognition mechanisms for transferred nucleic acids. Using commercially available fusogenic liposomes (Fuse-It-mRNA), we established highly efficient and fully biocompatible transfer of RNA molecules for in vitro as well as in vivo applications. We demonstrated bypassing of endosomal uptake routes and, therefore, of pattern recognition receptors that recognize nucleic acids with high efficiency. This may underlie the observed almost complete abolishment of inflammatory cytokine responses. RNA transfer experiments into zebrafish embryos and adult animals fully confirmed the functional mechanism and the wide range of applications from single cells to organisms.