ArticleScience advances2025
Replacing cholesterol and PEGylated lipids with zwitterionic ionizable lipids in LNPs for spleen-specific mRNA translation.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed.
- In vivo immune cell engineering from bench to clinical reality.Pharmaceutical science advances · 2026Review
- The advances and challenges of mRNA-LNP application in fields of hematology and oncology therapeutics.Journal of hematology & oncology · 2026Review
- Chemical and Biological Determinants of PEG-Lipid Shedding From Therapeutic Nanoparticles.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Structural evolution of ionizable lipids for nucleic acid delivery.Nature reviews. Chemistry · 2026Review
- Overcoming hepatic tropism: Precision engineering of lipid nanoparticles for extrahepatic RNA delivery.Materials today. Bio · 2026Review
- Ionizable Cholesterol-Integrated Lipid Nanoparticles for Efficient siRNA Delivery to Solid Tumors.ChemMedChem · 2026Article
- Zwitterion-Based Polymeric Carriers for Efficient Drug Delivery across Biological Barriers.Polymer science & technology (Washington, D.C.) · 2026Review
- Mechanical movements generated by movable lipids break endosomal barriers for enhanced mRNA therapeutics.Science advances · 2026Article
- Programming the immunological properties of mRNA vaccines for cancer.Nature reviews. Immunology · 2026Review
- Review
- Lipid Nanoparticle Surface Engineering with Heparosan Polysaccharides for Safe and Effective mRNA DeliveryACS applied materials & interfaces · 2026Article
- Functionalized Lipid Nanoparticles for Targeted RNA Delivery in Immune and Inflammatory Diseases.Biomedicines · 2026Review
- Advancements in RNA-based therapies from bench to bedside.npj drug discovery · 2026Review
- Targeted delivery platforms forFrontiers in pharmacology · 2026Review
- Engineering Anti-Tumor Immunity: An Immunological Framework for mRNA Cancer Vaccines.Vaccines · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors.
Funding
Abstract
The spleen is emerging as a key vaccination target. However, existing lipid nanoparticles (LNPs) primarily accumulate in the liver, limiting their efficacy in vaccine therapy. The cholesterol in current LNP formulations promotes their uptake by hepatocytes, while the polyethylene glycol-modified (PEGylated) lipids induce PEG immunogenicity, further reducing the efficacy in the setting of repeated administrations. We develop a three-component (ThrCo) LNP by replacing cholesterol and PEGylated lipids in Pfizer-BioNTech LNPs with zwitterionic pyridine carboxybetaine (PyCB) ionizable lipids (ILs), achieving ~70% lower liver accumulation and a 4.5-fold increase in spleen-specific mRNA translation. PyCB ILs enhance LNP hydrophilicity, stabilizing the outer membrane to compensate for cholesterol removal. PyCB groups also exhibit strong protonation at endosomal pH, facilitating mRNA translation. The zwitterionic surface of ThrCo LNP reduces protein adsorption, thereby preventing the accelerated blood clearance effect caused by PEGylated lipids following repeated administrations. Thus, ThrCo LNP-based vaccines efficiently deliver mRNA to splenic antigen-presenting cells, boosting immune responses and improving therapeutic outcomes.
Indexed as
Identifiers
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.