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. 2022 Dec 24;12(1):22293.
doi: 10.1038/s41598-022-26444-z.

Messenger RNA in lipid nanoparticles rescues HEK 293 cells from lipid-induced mitochondrial dysfunction as studied by real time pulse chase NMR, RTPC-NMR, spectroscopy

Nicholas Sciolino  1 , Sergey Reverdatto  1 , Aaron Premo  1 , Leonard Breindel  1 , Jianchao Yu  1 , Gregory Theophall  1 , David S Burz  1 , Anna Liu  2 , Todd Sulchek  2 , Ann Marie Schmidt  3 , Ravichandran Ramasamy  3 , Alexander Shekhtman  4
Affiliations

Messenger RNA in lipid nanoparticles rescues HEK 293 cells from lipid-induced mitochondrial dysfunction as studied by real time pulse chase NMR, RTPC-NMR, spectroscopy

Nicholas Sciolino et al. Sci Rep. .

Abstract

Analytical tools to study cell physiology are critical for optimizing drug-host interactions. Real time pulse chase NMR spectroscopy, RTPC-NMR, was introduced to monitor the kinetics of metabolite production in HEK 293T cells treated with COVID-19 vaccine-like lipid nanoparticles, LNPs, with and without mRNA. Kinetic flux parameters were resolved for the incorporation of isotopic label into metabolites and clearance of labeled metabolites from the cells. Changes in the characteristic times for alanine production implicated mitochondrial dysfunction as a consequence of treating the cells with lipid nanoparticles, LNPs. Mitochondrial dysfunction was largely abated by inclusion of mRNA in the LNPs, the presence of which increased the size and uniformity of the LNPs. The methodology is applicable to all cultured cells.

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