Smuggling on the Nanoscale—Fusogenic Liposomes Enable Efficient RNA-Transfer with Negligible Immune Response In Vitro and In Vivo
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 impairme...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/4/1210 |
| _version_ | 1827743943320666112 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Marco Hoffmann |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T04:37:54Z |
| format | Article |
| id | doaj.art-09b2dbc7f9744aafa81e8f90d6398fd5 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T04:37:54Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-09b2dbc7f9744aafa81e8f90d6398fd52023-11-17T20:54:17ZengMDPI AGPharmaceutics1999-49232023-04-01154121010.3390/pharmaceutics15041210Smuggling on the Nanoscale—Fusogenic Liposomes Enable Efficient RNA-Transfer with Negligible Immune Response In Vitro and In VivoMarco Hoffmann0Sven Gerlach1Masanari Takamiya2Samar Tarazi3Nils Hersch4Agnes Csiszár5Ronald Springer6Georg Dreissen7Hanno Scharr8Sepand Rastegar9Tanja Beil10Uwe Strähle11Rudolf Merkel12Bernd Hoffmann13IBI-2: Mechanobiology, Institute of Biological Information Processing, Forschungszentrum Jülich, 52428 Jülich, GermanyIBI-2: Mechanobiology, Institute of Biological Information Processing, Forschungszentrum Jülich, 52428 Jülich, GermanyInstitute of Biological and Chemical Systems-Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, GermanyIBI-2: Mechanobiology, Institute of Biological Information Processing, Forschungszentrum Jülich, 52428 Jülich, GermanyIBI-2: Mechanobiology, Institute of Biological Information Processing, Forschungszentrum Jülich, 52428 Jülich, GermanyIBI-2: Mechanobiology, Institute of Biological Information Processing, Forschungszentrum Jülich, 52428 Jülich, GermanyIBI-2: Mechanobiology, Institute of Biological Information Processing, Forschungszentrum Jülich, 52428 Jülich, GermanyIBI-2: Mechanobiology, Institute of Biological Information Processing, Forschungszentrum Jülich, 52428 Jülich, GermanyIAS-8: Data Analytics and Machine Learning, Institute for Advanced Simulation, Forschungszentrum Jülich, 52428 Jülich, GermanyInstitute of Biological and Chemical Systems-Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, GermanyInstitute of Biological and Chemical Systems-Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, GermanyInstitute of Biological and Chemical Systems-Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, GermanyIBI-2: Mechanobiology, Institute of Biological Information Processing, Forschungszentrum Jülich, 52428 Jülich, GermanyIBI-2: Mechanobiology, Institute of Biological Information Processing, Forschungszentrum Jülich, 52428 Jülich, GermanyThe 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.https://www.mdpi.com/1999-4923/15/4/1210fusogenic liposomesmammalian cellscortical tissuezebrafishRNA-transferlipofection |
| spellingShingle | 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 Smuggling on the Nanoscale—Fusogenic Liposomes Enable Efficient RNA-Transfer with Negligible Immune Response In Vitro and In Vivo Pharmaceutics fusogenic liposomes mammalian cells cortical tissue zebrafish RNA-transfer lipofection |
| title | Smuggling on the Nanoscale—Fusogenic Liposomes Enable Efficient RNA-Transfer with Negligible Immune Response In Vitro and In Vivo |
| title_full | Smuggling on the Nanoscale—Fusogenic Liposomes Enable Efficient RNA-Transfer with Negligible Immune Response In Vitro and In Vivo |
| title_fullStr | Smuggling on the Nanoscale—Fusogenic Liposomes Enable Efficient RNA-Transfer with Negligible Immune Response In Vitro and In Vivo |
| title_full_unstemmed | Smuggling on the Nanoscale—Fusogenic Liposomes Enable Efficient RNA-Transfer with Negligible Immune Response In Vitro and In Vivo |
| title_short | Smuggling on the Nanoscale—Fusogenic Liposomes Enable Efficient RNA-Transfer with Negligible Immune Response In Vitro and In Vivo |
| title_sort | smuggling on the nanoscale fusogenic liposomes enable efficient rna transfer with negligible immune response in vitro and in vivo |
| topic | fusogenic liposomes mammalian cells cortical tissue zebrafish RNA-transfer lipofection |
| url | https://www.mdpi.com/1999-4923/15/4/1210 |
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