ArticleNature biomedical engineering2026
Low reactogenicity and high tumour antigen expression from mRNA-LNPs with membrane-destabilizing zwitterionic lipids.
Article in Nature biomedical engineering, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 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
7 citing papers in PubMed.
- Macrophage programming in systemic sclerosis: Niches, networks, and translational horizons.Seminars in immunopathology · 2026Review
- Non-covalent assembly of multiple epitopes onto a single nanoparticle.Nature biomedical engineering · 2026Article
- Programming the immunological properties of mRNA vaccines for cancer.Nature reviews. Immunology · 2026Review
- Investigating Cerebello-Cortical Networks With EEG: Advances and Future Challenges.Cerebellum (London, England) · 2026Review
- An inflammation-targeted lipid nanoparticle inhibiting ferroptosis for spinal cord injury repair.Materials today. Bio · 2026Article
- Beyond conceptual advances in cancer therapies.Nature biomedical engineering · 2026Article
- Beyond conceptual advances in cancer therapies.Nature biomedical engineering · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors.
Funding
Abstract
Two key challenges in translating messenger RNA-based lipid nanoparticle (mRNA-LNP) cancer vaccines to clinical use are limited mRNA expression and unavoidable inflammatory responses. Here we develop a membrane-destabilizing zwitterionic ionizable lipid that enhances mRNA expression by promoting endosomal escape while reducing inflammatory reactogenicity. This lipid features a pyridine-based carboxybetaine (PyCB) zwitterionic headgroup, biodegradable multitailed alkyl chains and a tertiary amine linker. The PyCB headgroup forms a zwitterionic PyCB-water complex that protonates to a positively charged state below pH 6.8. This allows for good biocompatibility at physiological pH and strong protonation in endosomes, enabling earlier and more efficient mRNA release when synergistic with the tertiary amine and the tail moiety. Incorporating membrane-destabilizing zwitterionic lipids into the LNP formulation used in a commercially available mRNA vaccine significantly boosts mRNA expression in antigen-presenting cells within lymph nodes, enhancing cytotoxic T cell activation. In addition, these membrane-destabilizing zwitterionic lipid-containing nanoparticles show reduced inflammation and neutrophil infiltration at the injection site due to their zwitterionic property. These lipids are also compatible with existing targeted nanoparticle formulations, further improving mRNA delivery.
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.