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Overcoming analytical challenges to generate data critical to understanding lipid nanoparticle-delivered modified mRNA biodistribution.

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Aim: Chemically modified mRNA offers a novel approach to treat disease. Due to susceptibility to extracellular nucleases in vivo, dosed modified mRNA therapeutics can benefit from encapsulation within novel delivery… Click to show full abstract

Aim: Chemically modified mRNA offers a novel approach to treat disease. Due to susceptibility to extracellular nucleases in vivo, dosed modified mRNA therapeutics can benefit from encapsulation within novel delivery systems, such as lipid nanoparticles (LNPs). To understand the holistic effect of dosing LNP-encapsulated modified mRNA therapeutics can require bioanalysis of several components including the mRNA, protein and LNP. Methodology: These components can require bespoke preanalytical strategies to preserve analyte integrity to achieve successful analysis. Here we describe the sample collection, processing steps and bioanalytical technologies that can be used to overcome these challenges. Discussion: Understanding the biodistribution and holistic effects of the different components allow the pharmaceutical industry to evaluate safety and efficacy of modified mRNA therapeutics.

Keywords: biodistribution; modified mrna; overcoming analytical; analytical challenges; challenges generate; mrna therapeutics

Journal Title: Bioanalysis
Year Published: 2019

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