Journal Article

PUBDB-2025-02333

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Direct structural investigation of pH responsiveness in mRNA lipid nanoparticles: Refining paradigms

Wilhelmy, C. ; Uebbing, L. ; Kolb, B. ; Graewert, M. A. ; Nawroth, T. ; Haas, H. (Corresponding author)Extern*EMBL* ; Langguth, P. (Corresponding author)Extern*

2025
Elsevier New York, NY [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.jconrel.2025.113848  doi:10.3204/PUBDB-2025-02333

Abstract: Using small angle X-ray scattering measurements, structural coherencies in lipid nanoparticle (LNP) formulations comprising messenger RNA (mRNA) were elucidated in response to pH changes and as a function of RNA to lipid ratio. Formulations were assembled using selected ionizable lipids with well-known activity from previous experiments, with otherwise identical composition. Several structural parameters were determined, including internal organization, fraction of ordered material, the underlying repeating distance, and the fractal dimension of the overall particles. Repeat distances increased with increasing pH, with profiles similar to the shape of pKa curves, therefore allowing to directly reveal the structural implication of the pH responsiveness inside the particles. The fractal dimension, which so far had not been in the center of attention for quality control, was correlated with biological activity. Such systematic data on structure-function coherencies in LNPs can serve as complementary methods to standard lab-based quality control measures. This can help to facilitate and accelerate the rational formulation development of new RNA therapeutics.

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Contributing Institute(s):

1. EMBL-User (EMBL-User)
2. EMBL (EMBL)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)
2. 05K22UM3 - Pharma-SAXS: SAXS Instrumentierung zur Strukturspektrum Aufklärung von Lipid-basierten Nanopharmazeutika an DESY PETRA-P12 (BMBF-05K22UM3) (BMBF-05K22UM3)
3. SFB 1066 Z01 - Zentrale Aufgaben des Sonderforschungsbereichs (Z01) (239231186) (239231186)

Experiment(s):

1. PETRA Beamline P12 (PETRA III)

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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