Implementation of mRNA-Lipid Nanoparticle Technology in Atlantic Salmon ( Salmo salar ).

Autor:	Dahl LOS; Faculty of Veterinary Medicine, Norwegian University of Life Sciences, 1433 Ås, Norway., Hak S; Department of Biotechnology and Nanomedicine, SINTEF Industry, 7034 Trondheim, Norway., Braaen S; Faculty of Veterinary Medicine, Norwegian University of Life Sciences, 1433 Ås, Norway., Molska A; Department of Biotechnology and Nanomedicine, SINTEF Industry, 7034 Trondheim, Norway., Rodà F; Department of Biotechnology and Nanomedicine, SINTEF Industry, 7034 Trondheim, Norway.; Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41121 Modena, Italy.; IRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, Italy., Parot J; Department of Biotechnology and Nanomedicine, SINTEF Industry, 7034 Trondheim, Norway., Wessel Ø; Faculty of Veterinary Medicine, Norwegian University of Life Sciences, 1433 Ås, Norway., Fosse JH; Norwegian Veterinary Institute, 1433 Ås, Norway., Bjørgen H; Faculty of Veterinary Medicine, Norwegian University of Life Sciences, 1433 Ås, Norway., Borgos SE; Department of Biotechnology and Nanomedicine, SINTEF Industry, 7034 Trondheim, Norway., Rimstad E; Faculty of Veterinary Medicine, Norwegian University of Life Sciences, 1433 Ås, Norway.
Jazyk:	angličtina
Zdroj:	Vaccines [Vaccines (Basel)] 2024 Jul 18; Vol. 12 (7). Date of Electronic Publication: 2024 Jul 18.
DOI:	10.3390/vaccines12070788
Abstrakt:	Background: This study was conducted to investigate whether mRNA vaccine technology could be adapted for the ectothermic vertebrate Atlantic salmon ( Salmo salar ). Lipid nanoparticle (LNP) technology has been developed and optimized for mRNA vaccines in mammals, stabilizing mRNA and facilitating its delivery into cells. However, its utility at the temperatures and specific biological environments present in ectotherms remains unclear. In addition, it is unknown if modified mRNA containing non-canonical nucleotides can correctly translate in salmonid cells. Methods: We used an mRNA transcript coding for enhanced green fluorescence protein, flanked by the untranslated regions of the hemagglutinin-esterase gene of the infectious salmon anemia virus, and a 120-base-long poly(A) tail. The mRNA was generated via in vitro transcription where uridine residues were replaced with N1-methyl-pseudouridines, and then encapsulated in LNPs. Results: When transfected into the salmonid cell line CHH-1, the mRNA-LNP construct induced expression of EGFP. Furthermore, when mRNA-LNPs were injected intramuscularly into salmon, in vivo protein expression was demonstrated via immunohistochemistry. EGFP was observed in cells infiltrating the spaces between muscle cells in a focal inflammatory response. Conclusion: The results indicate that N1-methyl-pseudouridine-modified mRNA encapsulated in LNPs can be used to express antigens of interest in salmonid fish.
Databáze:	MEDLINE
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