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Linkage between end...
Linkage between endosomal escape of LNP-mRNA and loading into EVs for transport to other cells
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- Marco, Maugeri, 1983 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Nawaz, Muhammad (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Papadimitriou, Alexandros (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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Angerfors, Annelie (author)
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- Camponeschi, Alessandro (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Na, Manli (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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Hölttä, Mikko (author)
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Skantze, Pia (author)
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Johansson, Svante (author)
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- Sundqvist, Martina (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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Lindquist, Johnny (author)
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Kjellman, Tomas (author)
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- Mårtensson, Inga-Lill, 1957 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Jin, Tao, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Sunnerhagen, Per, 1959 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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Östman, Sofia (author)
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Lindfors, Lennart (author)
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- Valadi, Hadi, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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(creator_code:org_t)
- 2019-09-24
- 2019
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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https://gup.ub.gu.se...
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Abstract
Subject headings
Close
- RNA-based therapeutics hold great promise for treating diseases and lipid nanoparticles (LNPs) represent the most advanced platform for RNA delivery. However, the fate of the LNP-mRNA after endosome-engulfing and escape from the autophagy-lysosomal pathway remains unclear. To investigate this, mRNA (encoding human erythropoietin) was delivered to cells using LNPs, which shows, for the first time, a link between LNP-mRNA endocytosis and its packaging into extracellular vesicles (endo-EVs: secreted after the endocytosis of LNP-mRNA). Endosomal escape of LNP-mRNA is dependent on the molar ratios between ionizable lipids and mRNA nucleotides. Our results show that fractions of ionizable lipids and mRNA (1:1 molar ratio of hEPO mRNA nucleotides:ionizable lipids) of endocytosed LNPs were detected in endo-EVs. Importantly, these EVs can protect the exogenous mRNA during in vivo delivery to produce human protein in mice, detected in plasma and organs. Compared to LNPs, endo-EVs cause lower expression of inflammatory cytokines.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- Extracellular vesicles
- Exosomes
- mRNA therapy
Publication and Content Type
- ref (subject category)
- art (subject category)
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Marco, Maugeri, ...
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Nawaz, Muhammad
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Papadimitriou, A ...
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Angerfors, Annel ...
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Camponeschi, Ale ...
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Na, Manli
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Hölttä, Mikko
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Skantze, Pia
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Johansson, Svant ...
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Sundqvist, Marti ...
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Lindquist, Johnn ...
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Kjellman, Tomas
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Mårtensson, Inga ...
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Jin, Tao, 1973
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Sunnerhagen, Per ...
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Östman, Sofia
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Lindfors, Lennar ...
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Valadi, Hadi, 19 ...
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Nature Communica ...
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University of Gothenburg