ArticleCommunications biology2021
Ionization and structural properties of mRNA lipid nanoparticles influence expression in intramuscular and intravascular administration.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 206 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
206 citing papers in PubMed, 387 citations in OpenAlex.
- Targeted delivery of mRNA to immune cells forDrug delivery · 2026Review
- Exploration of biodistribution of mRNA-delivering lipid nanoparticles in the neonatal mouse inner ear.International journal of pharmaceutics: X · 2026Article
- In vivo engineering of CAR natural killer cells for immunotherapy using ligand-directed lipid nanoparticles.Nature biotechnology · 2026Article
- Structural evolution of ionizable lipids for nucleic acid delivery.Nature reviews. Chemistry · 2026Review
- Dual pKa Lipid Nanoparticles for Lung-tropic mRNA Delivery and pH-Programmed Endosomal Escape.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Design and development of lipid nanoparticle formulations for brain gene therapy.Molecular therapy. Nucleic acids · 2026Article
- Systemically delivered mRNA-LNPs transfect primary and secondary liver tumors.Molecular therapy. Nucleic acids · 2026Article
- Hydrophobic Tail and Linker Diversification of PEG-Lipids Unlocks Precise Muscle Tropism of mRNA-Lipid Nanoparticles.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Improved specificity and efficiency of in vivo adenine base editing therapies with hybrid guide RNAs.Nature biomedical engineering · 2026Article
- RNA Size and Structure Modulate the Apparent pKa of Ionizable Lipid Nanoparticles.Bioconjugate chemistry · 2026Article
- Critical chemistry manufacturing and controls considerations for mRNA lipid nanoparticle translation.Discover nano · 2026Review
- Membrane environment sets the functional pKBiophysical journal · 2026Article
- Resolving Heterogeneity of Targeted Lipid Nanoparticles Through Solution-Based Biophysical Analyses.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Overcoming size barriers in retinal gene therapy via lipid nanoparticle-mediated delivery of full-length eys DNA.Drug delivery and translational research · 2026Article
- Immunological Evaluation of mRNA-LNP Vaccines Targeting Conserved S2 and NSP3 Domains of SARS-CoV-2.Biotechnology journal · 2026Article
- Post-loading ribonucleic acid into lipid nanoparticle carriers.bioRxiv : the preprint server for biology · 2026Article
- From Morphology to Mechanism: Cryo-Electron Microscopy Insights into Lipid Nanoparticles for RNA Delivery.ACS nano · 2026Review
- Review
- Article
- Endogenous targeting lipid nanoparticles for systemic mRNA delivery to lung cancer tumors.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
146 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipid Nanoparticles (LNPs) are used to deliver siRNA and COVID-19 mRNA vaccines. The main factor known to determine their delivery efficiency is the pKa of the LNP containing an ionizable lipid. Herein, we report a method that can predict the LNP pKa from the structure of the ionizable lipid. We used theoretical, NMR, fluorescent-dye binding, and electrophoretic mobility methods to comprehensively measure protonation of both the ionizable lipid and the formulated LNP. The pKa of the ionizable lipid was 2-3 units higher than the pKa of the LNP primarily due to proton solvation energy differences between the LNP and aqueous medium. We exploited these results to explain a wide range of delivery efficiencies in vitro and in vivo for intramuscular (IM) and intravascular (IV) administration of different ionizable lipids at escalating ionizable lipid-to-mRNA ratios in the LNP. In addition, we determined that more negatively charged LNPs exhibit higher off-target systemic expression of mRNA in the liver following IM administration. This undesirable systemic off-target expression of mRNA-LNP vaccines could be minimized through appropriate design of the ionizable lipid and LNP.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.