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Transfection Potency of Lipid Nanoparticles Containing mRNA Depends on Relative Loading Levels

2024/12/31 by Suiyang Liao, Shuangyu Wang, Abishek Wadhwa +13 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Lipid Membrane Structure and Behavior #RNA Interference and Gene Delivery #RNA and protein synthesis mechanisms

paper · pdf · doi:10.1021/acsami.4c20077

openalex publication_date 2024/12/31 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/04

Abstract

High Resolution Image Download MS PowerPoint Slide When formulating mRNA into lipid nanoparticles (LNP), various copy numbers of mRNA are encapsulated, leading to a distribution of mRNA loading levels within the LNPs. It is unclear whether the mRNA loading level affects the functional delivery of the message. Here we show that depending on the mRNA loading level, LNPs exhibit distinct mass densities and can be fractionated via ultracentrifugation. Upon fractionation, we investigated if mRNA loading levels influence LNP sizing, lipid composition, and morphology. We further conducted in vitro and in vivo functional delivery of mRNA and found that the LNP fraction with the highest mRNA loading levels was the least transfection competent.

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