Ex Vivo Delivery of mRNA to Immune Cells via a Nonendosomal Route Obviates the Need for Nucleoside Modification

Ghoshal, B and Chakraborty, D and Nag, M and Varadarajan, R and Jhunjhunwala, S (2024) Ex Vivo Delivery of mRNA to Immune Cells via a Nonendosomal Route Obviates the Need for Nucleoside Modification. In: ACS Bio and Med Chem Au .

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Abstract

Base modification and the use of lipid nanoparticles are thought to be essential for efficient in vivo delivery and expression of mRNA. However, for ex vivo immune cell engineering, the need for either of the two is unclear. Previous reports have suggested that nucleic acids may be efficiently delivered to immune cells ex vivo, through a nonendosomal delivery route, but the need for base modification has not been determined. Herein, we demonstrate that when a nonendosomal delivery method is used, unmodified mRNA performs equally well to the commonly used base-modified mRNA, including the N1 methyl pseudouridine modification, in terms of protein expression and inflammatory response in cells. However, if an endosomal delivery route is used, then N1 methyl pseudouridine modification is necessary for high expression and low inflammatory response, as demonstrated by others as well. Overall, we show that nonendosomal mRNA delivery renders nucleoside modifications nonessential and that unmodified mRNA combined with nonendosomal delivery route may be used for efficient ex vivo mRNA-based engineering of immune cells. © 2024 The Authors. Published by American Chemical Society

Item Type:	Journal Article
Publication:	ACS Bio and Med Chem Au
Publisher:	American Chemical Society
Additional Information:	The copyright for this article belongs to American Chemical Society
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited:	09 Dec 2024 17:47
Last Modified:	09 Dec 2024 17:47
URI:	http://eprints.iisc.ac.in/id/eprint/87079

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