ArticleNature communications2020
Naturally-occurring cholesterol analogues in lipid nanoparticles induce polymorphic shape and enhance intracellular delivery of mRNA.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 287 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
287 citing papers in PubMed, 528 citations in OpenAlex.
- Optimization of lipid nanoparticles reduces hepatic accumulation and enhances local delivery of mRNA.Science China. Life sciences · 2026Article
- Bioengineering strategies for improving the immunogenicity of mRNA vaccines.Signal transduction and targeted therapy · 2026Review
- Bioactive lipid-derived nanoparticles for RNA delivery.Materials today (Kidlington, England) · 2026Article
- Overcoming hepatic tropism: Precision engineering of lipid nanoparticles for extrahepatic RNA delivery.Materials today. Bio · 2026Review
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- Engineering mRNA-LNP Medicines for the Ageing Brain: Opportunities and Challenges for Neurodegenerative Diseases.Exploration (Beijing, China) · 2026Review
- pH-Sensitive Amino Lipid-Driven Pore Formation Enables Endosomal Escape of Lipid Nanoparticles.Nature communications · 2026Article
- Engineering the Future of Precision Medicine: A Comprehensive Guide to RNA Therapeutics.Current issues in molecular biology · 2026Review
- Delivering the future of immunotherapy: A state-of-the-art review of gene editing in immune cells with lipid nanoparticles.Materials today. Bio · 2026Review
- Resolving Heterogeneity of Targeted Lipid Nanoparticles Through Solution-Based Biophysical Analyses.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Construction of a translational whole-body physiologically based pharmacokinetic model to investigate the biodistribution of lipid nanoparticle-based mRNA therapeutics for intracellular protein targets.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Mechanical insights into regulation of bio-nano interactions for lipid-based nanocarriers.Discover nano · 2026Review
- From Morphology to Mechanism: Cryo-Electron Microscopy Insights into Lipid Nanoparticles for RNA Delivery.ACS nano · 2026Review
- The membrane distal domain of CD16a allosterically regulates NK cell ADCC.bioRxiv : the preprint server for biology · 2026Article
- Precision engineering of macrophage reprogramming with RNA interference-loaded lipid nanoparticles: a game-changer in cancer immunotherapy.Drug delivery and translational research · 2026Review
- Nanotechnology-mediated precision delivery of mRNA.Nature materials · 2026Review
- Multiscale modeling guided potency assessment of mRNA-lipid nanoparticles.Molecular therapy. Nucleic acids · 2026Article
- From LNPs to hybrid nanocarriers: development, challenges and redesign of non-viral gene delivery.Journal of nanobiotechnology · 2026Review
- Cholesterol analogs modulate lipid nanoparticle performance for mRNA delivery after lyophilization and enable ocular disease therapy.Materials today. Bio · 2026Article
- Decoding Undesirable Inflammatory Responses of Nucleic Acid-Delivering Lipid Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
227 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Endosomal sequestration of lipid-based nanoparticles (LNPs) remains a formidable barrier to delivery. Herein, structure-activity analysis of cholesterol analogues reveals that incorporation of C-24 alkyl phytosterols into LNPs (eLNPs) enhances gene transfection and the length of alkyl tail, flexibility of sterol ring and polarity due to -OH group is required to maintain high transfection. Cryo-TEM displays a polyhedral shape for eLNPs compared to spherical LNPs, while x-ray scattering shows little disparity in internal structure. eLNPs exhibit higher cellular uptake and retention, potentially leading to a steady release from the endosomes over time. 3D single-particle tracking shows enhanced intracellular diffusivity of eLNPs relative to LNPs, suggesting eLNP traffic to productive pathways for escape. Our findings show the importance of cholesterol in subcellular transport of LNPs carrying mRNA and emphasize the need for greater insights into surface composition and structural properties of nanoparticles, and their subcellular interactions which enable designs to improve endosomal escape.
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What OpenQuestion holds
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.