• Structural characterization of...

Treffer: Structural characterization of mRNA lipid nanoparticles (LNPs) in the presence of mRNA-free LNPs.

Title:
Structural characterization of mRNA lipid nanoparticles (LNPs) in the presence of mRNA-free LNPs.
Authors:
Chen X; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150086, China; Institute of Natural Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; School of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai 200240, China., Ye Y; Institute of Natural Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; School of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai 200240, China., Li M; Institute of Natural Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; School of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai 200240, China., Zuo T; Spallation Neutron Source Science Center, Dongguan 523803, China; Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China., Xie Z; Spallation Neutron Source Science Center, Dongguan 523803, China; Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China., Ke Y; Spallation Neutron Source Science Center, Dongguan 523803, China; Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China., Cheng H; Spallation Neutron Source Science Center, Dongguan 523803, China; Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China., Hong L; Institute of Natural Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; School of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai 200240, China; Shanghai National Centre for Applied Mathematics (SJTU Center), MOE-LSC, Shanghai Jiao Tong University, Shanghai 200240, China; Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 201203, China. Electronic address: hongl3liang@sjtu.edu.cn., Liu Z; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150086, China; Institute of Natural Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; Shanghai National Centre for Applied Mathematics (SJTU Center), MOE-LSC, Shanghai Jiao Tong University, Shanghai 200240, China; Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 201203, China. Electronic address: liuzhuo_jude@126.com.
Source:
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2025 Oct 10; Vol. 386, pp. 114082. Date of Electronic Publication: 2025 Jul 31.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE
Imprint Name(s):
Original Publication: Amsterdam : Elsevier Science Publishers, 1984-
MeSH Terms:
RNA, Messenger*/chemistry , Liposomes*/chemistry , Nanoparticles*/chemistry, Nanoparticle Drug Delivery System ; Models, Structural ; mRNA Vaccines ; Scattering, Small Angle ; Neutron Diffraction
Contributed Indexing:
Keywords: Nano flow cytometry; Small angle neutron scattering; mRNA lipid nanoparticles; mRNA-free LNPs
Substance Nomenclature:
0 (RNA, Messenger)
0 (Lipid Nanoparticles)
0 (Liposomes)
0 (Nanoparticle Drug Delivery System)
0 (mRNA Vaccines)
Entry Date(s):
Date Created: 20250802 Date Completed: 20251218 Latest Revision: 20251218
Update Code:
20251218
DOI:
10.1016/j.jconrel.2025.114082
PMID:
40752860
Database:
MEDLINE

Weitere Informationen

Lipid nanoparticles (LNPs) have emerged as a versatile platform for mRNA delivery across a range of applications, including disease prevention, cancer immunotherapy, and gene editing. Structural models of mRNA lipid nanoparticles (mRNA-LNPs) have also been proposed based on characterization of samples by using various advanced techniques. Among these, small angle neutron scattering (SANS) has proven essential for elucidating the lipid distribution within mRNA-LNPs, a factor crucial to both their preparation and efficacy. However, recent findings suggest that the mRNA-LNP samples prepared via commercial microfluidic techniques may contain a substantial fraction of mRNA-free LNPs, casting doubt on the validity of earlier structural models. In this study, we employed contrast variation SANS to characterize both mRNA-free LNPs and our mRNA-LNP sample, and quantified the proportion of mRNA-free LNPs present to be ∼30 % in our mRNA-LNP sample using nano flow cytometry. By removing the contributions of mRNA-free LNPs from the SANS data of our mRNA-LNP sample, we were able to precisely characterize the structure of mRNA-loaded LNPs. Consequently, we proposed structural models for both mRNA-free and mRNA-loaded LNPs. Notably, our analysis revealed similar lipid distributions and shell thicknesses between the two particle types, while the solvent content in mRNA-loaded LNPs was significantly higher, leading to a larger core size. This work not only offers a method for accurately characterizing the structure of mRNA-loaded LNPs, but also establishes criteria for selecting appropriate analytical techniques based on the structural parameters of interest. Therefore, our findings hold significant implications for the mechanistic understanding and quality control of mRNA-based vaccines.
(Copyright © 2025 Elsevier B.V. All rights reserved.)

Declaration of competing interest The authors declare no competing financial interest.