ArticleACS nano2019
The Skin You Are In: Design-of-Experiments Optimization of Lipid Nanoparticle Self-Amplifying RNA Formulations in Human Skin Explants.
Article in ACS nano, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 68 citations in OpenAlex.
- Acne: epidemiology, risk factors, pathogenesis, management and cutting-edge research.Signal transduction and targeted therapy · 2026Review
- New approach methodologies (NAMs) for preclinical and translational evaluation of mRNA-lipid nanoparticle (LNP) therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2026Review
- Lipid nanoparticle formulations including stereochemically defined glycomacromolecules for delivery of saRNA.Chemical science · 2026Article
- Unique Aerofoil-Structured Microfluidics for High Throughput Lipid Nanoparticle Formulation Screening and Scale-up.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Boosting LNP Performance: Higher Concentrations of Lipid Mixtures Improve In Vivo Gene Expression and Storage Stability.Pharmaceutics · 2025Article
- Immunology of RNA-based vaccines: The critical interplay between inflammation and expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- RNA vaccines: The dawn of a new age for tuberculosis?Human vaccines & immunotherapeutics · 2025Review
- Alphaviral backbone of self-amplifying RNA enhances protein expression and immunogenicity against SARS-CoV-2 antigen.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Transfer learning Bayesian optimization for competitor DNA molecule design for use in diagnostic assays.Biotechnology and bioengineering · 2025Article
- Immune Cells Phenotypes and Causal Relationship with Acne Vulgaris: Insights from Mendelian Randomization.Clinical, cosmetic and investigational dermatology · 2025Article
- Advances in molecular imaging and targeted therapeutics for lymph node metastasis in cancer: a comprehensive review.Journal of nanobiotechnology · 2024Review
- Navigating the intricate in-vivo journey of lipid nanoparticles tailored for the targeted delivery of RNA therapeutics: a quality-by-design approach.Journal of nanobiotechnology · 2024Review
- Transfer Learning Bayesian Optimization to Design Competitor DNA Molecules for Use in Diagnostic Assays.ArXiv · 2024Article
- Design of Experiments Grants Mechanistic Insights into the Synthesis of Spermine-Containing PBAE Copolymers.ACS applied materials & interfaces · 2024Article
- Composition of lipid nanoparticles for targeted delivery: application to mRNA therapeutics.Frontiers in pharmacology · 2024Review
- Association of different cell types and inflammation in early acne vulgaris.Frontiers in immunology · 2024Review
- Unlocking the Therapeutic Applicability of LNP-mRNA: Chemistry, Formulation, and Clinical Strategies.Research (Washington, D.C.) · 2024Review
- Quality by Design (QbD) and Design of Experiments (DOE) as a Strategy for Tuning Lipid Nanoparticle Formulations for RNA Delivery.Biomedicines · 2023Review
- Throughput-scalable manufacturing of SARS-CoV-2 mRNA lipid nanoparticle vaccines.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Effect of Cryoprotectants and Storage Conditions on the Transfection Efficiency, Stability, and Safety of Lipid-Based Nanoparticles for mRNA and DNA Delivery.Advanced healthcare materials · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Messenger RNA (mRNA) is a promising tool for biotherapeutics, and self-amplifying mRNA (saRNA) is particularly advantageous, because it results in abundant protein expression and production is easily scalable. While mRNA therapeutics have been shown to be highly effective in small animals, the outcomes do not scale linearly when these formulations are translated to dose-escalation studies in humans. Here, we utilize a design of experiments (DoE) approach to optimize the formulation of saRNA lipid nanoparticles in human skin explants. We first observed that luciferase expression from saRNA peaked after 11 days in human skin. Using DoE inputs of complexing lipid identity, lipid nanoparticle dose, lipid concentration, particle concentration, and ratio of zwitterionic to cationic lipids, we optimized the saRNA-induced luciferase expression in skin explants. Lipid identity and lipid concentration were found to be significant parameters in the DoE model, and the optimized formulation resulted in ∼7-fold increase in luciferase expression, relative to initial 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) formulation. Using flow cytometry, we observed that optimized formulations delivered the saRNA to ∼2% of the resident cells in the human skin explants. Although immune cells comprise only 7% of the total population of cells in skin, immune cells were found to express ∼50% of the RNA. This study demonstrates the powerful combination of using a DoE approach paired with clinically relevant human skin explants to optimize nucleic acid formulations. We expect that this system will be useful for optimizing both formulation and molecular designs of clinically translational nucleic acid vaccines and therapeutics.
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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.