ArticleBioengineering & translational medicine2023
Optimization of ionizable lipids for aerosolizable mRNA lipid nanoparticles.
Article in Bioengineering & translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 27 citations in OpenAlex.
- Structural evolution of ionizable lipids for nucleic acid delivery.Nature reviews. Chemistry · 2026Review
- Target-Product and Translational Design Principles for Inhalable RNA Nanomedicines.Pharmaceutics · 2026Review
- Sulfonium lipid nanoparticles for intranasal mRNA delivery to lung epithelial and immune cells.Acta biomaterialia · 2025Article
- Nebulization of an mRNA-encoded monoclonal antibody for passive immunization of foals against Rhodococcus equi.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Robust peptide/RNA complexes prepared with microfluidic mixing for pulmonary delivery by nebulisation.Drug delivery and translational research · 2025Article
- Customizable Polymeric Nanoparticle Materials Optimized on Hypoxic Cells Facilitate mRNA Expression in the Lungs In Vivo.Advanced healthcare materials · 2025Article
- Investigation of the impact of lipid nanoparticle compositions on the delivery and T cell response of circRNA vaccine.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Recent strategies for enhanced delivery of mRNA to the lungs.Nanomedicine (London, England) · 2025Review
- Analysis of Polymer/siRNA Nanoparticle Efficacy and Biocompatibility in 3D Air-Liquid Interface Culture Compared to 2D Cell Culture.Pharmaceutics · 2025Article
- Nanoparticle-Mediated siRNA Delivery in Human Epithelial Lung Cells Cultured at the Air-Liquid Interface.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Discovery of peptides for ligand-mediated delivery of mRNA lipid nanoparticles to cystic fibrosis lung epithelia.Molecular therapy. Nucleic acids · 2024Article
- Respiratory delivered vaccines: Current status and perspectives in rational formulation design.Acta pharmaceutica Sinica. B · 2024Review
- Review
- Optimization of ionizable lipids for aerosolizable mRNA lipid nanoparticles.Bioengineering & translational medicine · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although mRNA lipid nanoparticles (LNPs) are highly effective as vaccines, their efficacy for pulmonary delivery has not yet fully been established. A major barrier to this therapeutic goal is their instability during aerosolization for local delivery. This imparts a shear force that degrades the mRNA cargo and therefore reduces cell transfection. In addition to remaining stable upon aerosolization, mRNA LNPs must also possess the aerodynamic properties to achieve deposition in clinically relevant areas of the lungs. We addressed these challenges by formulating mRNA LNPs with SM-102, the clinically approved ionizable lipid in the Spikevax COVID-19 vaccine. Our lead candidate, B-1, had the highest mRNA expression in both a physiologically relevant air-liquid interface (ALI) human lung cell model and in healthy mice lungs upon aerosolization. Further, B-1 showed selective transfection in vivo of lung epithelial cells compared to immune cells and endothelial cells. These results show that the formulation can target therapeutically relevant cells in pulmonary diseases such as cystic fibrosis. Morphological studies of B-1 revealed differences in the surface structure compared to LNPs with lower transfection efficiency. Importantly, the formulation maintained critical aerodynamic properties in simulated human airways upon next generation impaction. Finally, structure-function analysis of SM-102 revealed that small changes in the number of carbons can improve upon mRNA delivery in ALI human lung cells. Overall, our study expands the application of SM-102 and its analogs to aerosolized pulmonary delivery and identifies a potent lead candidate for future therapeutically active mRNA therapies.
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.