Selectively expressed RNA molecules as a versatile tool for functionalized cell targeting
Abstract Targeting of diseased cells is one of the most urgently needed prerequisites for a next generation of potent pharmaceuticals. Different approaches pursued fail mainly due to a lack of specific surface markers. Developing an RNA-based methodology, we can now ensure precise cell targeting com...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55547-6 |
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| author | Frederik Rastfeld Marco Hoffmann Sylvie Krüger Patrick Bohn Anne-Sophie Gribling-Burrer Laura Wagner Nils Hersch Carina Stegmayr Lukas Lövenich Sven Gerlach Daniel Köninger Christina Hoffmann Helene L. Walter Dirk Wiedermann Hajaani Manoharan Gereon R. Fink Rudolf Merkel Heribert Bohlen Redmond P. Smyth Maria A. Rueger Bernd Hoffmann |
| author_facet | Frederik Rastfeld Marco Hoffmann Sylvie Krüger Patrick Bohn Anne-Sophie Gribling-Burrer Laura Wagner Nils Hersch Carina Stegmayr Lukas Lövenich Sven Gerlach Daniel Köninger Christina Hoffmann Helene L. Walter Dirk Wiedermann Hajaani Manoharan Gereon R. Fink Rudolf Merkel Heribert Bohlen Redmond P. Smyth Maria A. Rueger Bernd Hoffmann |
| author_sort | Frederik Rastfeld |
| collection | DOAJ |
| description | Abstract Targeting of diseased cells is one of the most urgently needed prerequisites for a next generation of potent pharmaceuticals. Different approaches pursued fail mainly due to a lack of specific surface markers. Developing an RNA-based methodology, we can now ensure precise cell targeting combined with selective expression of effector proteins for therapy, diagnostics or cell steering. The specific combination of the molecular properties of antisense technology and mRNA therapy with functional RNA secondary structures allowed us to develop selectively expressed RNA molecules for medical applications. These seRNAs remain inactive in non-target cells and induce translation by partial degradation only in preselected cell types of interest. Cell specificity and type of functionalization are easily adaptable based on a modular system. In proof-of-concept studies we use seRNAs as platform technology for highly selective cell targeting. We effectively treat breast tumor cell clusters in mixed cell systems and shrink early U87 glioblastoma cell clusters in the brain of male mice without detectable side effects. Our data open up potential avenues for various therapeutic applications. |
| format | Article |
| id | doaj-art-c99d912cd57241fa80546cc5718dda26 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-c99d912cd57241fa80546cc5718dda262025-01-12T12:31:31ZengNature PortfolioNature Communications2041-17232025-01-0116111710.1038/s41467-024-55547-6Selectively expressed RNA molecules as a versatile tool for functionalized cell targetingFrederik Rastfeld0Marco Hoffmann1Sylvie Krüger2Patrick Bohn3Anne-Sophie Gribling-Burrer4Laura Wagner5Nils Hersch6Carina Stegmayr7Lukas Lövenich8Sven Gerlach9Daniel Köninger10Christina Hoffmann11Helene L. Walter12Dirk Wiedermann13Hajaani Manoharan14Gereon R. Fink15Rudolf Merkel16Heribert Bohlen17Redmond P. Smyth18Maria A. Rueger19Bernd Hoffmann20Institute of Biological Information Processing, IBI-2: Mechanobiology, Research Centre JuelichInstitute of Biological Information Processing, IBI-2: Mechanobiology, Research Centre JuelichInstitute of Biological Information Processing, IBI-2: Mechanobiology, Research Centre JuelichHelmholtz Institute for RNA-based Infection Research, Helmholtz Centre for Infection ResearchHelmholtz Institute for RNA-based Infection Research, Helmholtz Centre for Infection ResearchInstitute of Biological Information Processing, IBI-2: Mechanobiology, Research Centre JuelichInstitute of Biological Information Processing, IBI-2: Mechanobiology, Research Centre JuelichInstitute of Neuroscience and Medicine, INM-4: Medical Imaging Physics, Research Centre JuelichInstitute of Biological Information Processing, IBI-2: Mechanobiology, Research Centre JuelichInstitute of Biological Information Processing, IBI-2: Mechanobiology, Research Centre JuelichInstitute of Biological Information Processing, IBI-2: Mechanobiology, Research Centre JuelichInstitute of Biological Information Processing, IBI-2: Mechanobiology, Research Centre JuelichInstitute of Neuroscience and Medicine, INM-3: Cognitive Neuroscience, Research Centre JuelichMax Planck Institute for Metabolism Research, Multimodal Imaging GroupInstitute of Biological Information Processing, IBI-2: Mechanobiology, Research Centre JuelichInstitute of Neuroscience and Medicine, INM-3: Cognitive Neuroscience, Research Centre JuelichInstitute of Biological Information Processing, IBI-2: Mechanobiology, Research Centre JuelichSRTD biotech GmbHHelmholtz Institute for RNA-based Infection Research, Helmholtz Centre for Infection ResearchInstitute of Neuroscience and Medicine, INM-3: Cognitive Neuroscience, Research Centre JuelichInstitute of Biological Information Processing, IBI-2: Mechanobiology, Research Centre JuelichAbstract Targeting of diseased cells is one of the most urgently needed prerequisites for a next generation of potent pharmaceuticals. Different approaches pursued fail mainly due to a lack of specific surface markers. Developing an RNA-based methodology, we can now ensure precise cell targeting combined with selective expression of effector proteins for therapy, diagnostics or cell steering. The specific combination of the molecular properties of antisense technology and mRNA therapy with functional RNA secondary structures allowed us to develop selectively expressed RNA molecules for medical applications. These seRNAs remain inactive in non-target cells and induce translation by partial degradation only in preselected cell types of interest. Cell specificity and type of functionalization are easily adaptable based on a modular system. In proof-of-concept studies we use seRNAs as platform technology for highly selective cell targeting. We effectively treat breast tumor cell clusters in mixed cell systems and shrink early U87 glioblastoma cell clusters in the brain of male mice without detectable side effects. Our data open up potential avenues for various therapeutic applications.https://doi.org/10.1038/s41467-024-55547-6 |
| spellingShingle | Frederik Rastfeld Marco Hoffmann Sylvie Krüger Patrick Bohn Anne-Sophie Gribling-Burrer Laura Wagner Nils Hersch Carina Stegmayr Lukas Lövenich Sven Gerlach Daniel Köninger Christina Hoffmann Helene L. Walter Dirk Wiedermann Hajaani Manoharan Gereon R. Fink Rudolf Merkel Heribert Bohlen Redmond P. Smyth Maria A. Rueger Bernd Hoffmann Selectively expressed RNA molecules as a versatile tool for functionalized cell targeting Nature Communications |
| title | Selectively expressed RNA molecules as a versatile tool for functionalized cell targeting |
| title_full | Selectively expressed RNA molecules as a versatile tool for functionalized cell targeting |
| title_fullStr | Selectively expressed RNA molecules as a versatile tool for functionalized cell targeting |
| title_full_unstemmed | Selectively expressed RNA molecules as a versatile tool for functionalized cell targeting |
| title_short | Selectively expressed RNA molecules as a versatile tool for functionalized cell targeting |
| title_sort | selectively expressed rna molecules as a versatile tool for functionalized cell targeting |
| url | https://doi.org/10.1038/s41467-024-55547-6 |
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