Gauging lipid vulnerabilities in mRNA-LNPs under various environmental stressors through TIMS-TOF analysis

RSC Advances 2026 Open access

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Authors: Michael Girgis, Amir M. Saed, Suman Alishetty, Manuel Carrasco, Dillon O'Neill, Nabilah Ibnat Baby, Gregory Petruncio, Caroline D. Hoemann, Mathew Albano, Xuejun Peng, Beixi Wang, Erica M. Forsberg
+3 more Mohammad Nazim Rahil, Amany A. Saleh, Mikell Paige
DOI: 10.1039/d5ra08835f
Cited by: 4
References: 68

Abstract

-glycero-3-phosphocholine (DSPC). These modifications occur at levels and sites consistent with impaired endosomal escape chemistry, despite preservation of particle size, encapsulation efficiency, and conventional biophysical readouts. By directly linking defined environmental stressors to discrete ionizable lipid oxidation pathways, this work provides a mechanistic framework for understanding hidden failure modes in mRNA LNP formulations and establishes UHPLC-TIMS-TOF MS as a powerful tool for predictive stability assessment and rational design of more robust, regulation-ready mRNA therapeutics.

Fields of Study & Subjects

Lipid Membrane Structure and Behavior RNA Interference and Gene Delivery RNA Research and Splicing

Publication details

Journal / source
RSC Advances
Publisher
Royal Society of Chemistry (RSC)
Volume
16
Issue
21
Pages
18984–18994
Publication date
1 January 2026
Language
EN