ArticleMolecular pharmaceutics2022
Optimization of Lipid Nanoparticles for saRNA Expression and Cellular Activation Using a Design-of-Experiment Approach.
Article in Molecular pharmaceutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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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
44 citing papers in PubMed.
- From RNA design to delivery: Computational strategies for functional RNA therapeutics.Bioactive materials · 2027Review
- Lipid nanoparticles optimized for large RNA cargo and tissue targeting enhance in vivo genome editing.Nature biotechnology · 2026Article
- Transgene sequence codon optimization and composition determines replication competence of self-amplifying RNA.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Advancements of mRNA-lipid nanoparticle links to gene editing and immune responses.Journal, genetic engineering & biotechnology · 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
- Genetic Medicine Approaches for Tumor Suppressor Loss: Therapeutic Replacement with Self-Amplifying RNA.Pharmaceutical research · 2026Review
- Mycobacterium tuberculosis-induced PCBP1 degradation drives macrophage ferroptosis to promote infection: a lung-macrophage-targeted RNAa nanotherapy.Journal of nanobiotechnology · 2026Article
- Gene therapy for liver diseases: methods, challenges and opportunities.Journal of nanobiotechnology · 2026Review
- A multiobjective AI model for LNP engineering enhances tissue-selective mRNA delivery.Nature biotechnology · 2026Article
- Industrial Perspective on the Manufacturing of Lipid Nanoparticles for Nucleic Acid Delivery.Pharmaceutics · 2026Review
- Amino acid-derived ionizable lipids enable inhaled base editing for therapeutic gene correction in the lung.Nature materials · 2026Article
- Article
- Plasmid DNA Delivery Using a Stable Nanovesicle Platform: A Design-of-Experiments-Guided Investigation.ACS biomaterials science & engineering · 2026Article
- Nanotechnology-Enhanced Vaccines for Respiratory Infections: Opportunities and Challenges.International journal of nanomedicine · 2026Review
- Investigation of in vitro delivery conditions for self-amplifying mRNA.Bioprocess and biosystems engineering · 2025Article
- Divergent Delivery and Expression Kinetics of Lipid and Polymeric Nanoparticles across mRNA Modalities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Microfluidic and Turbulent Mixing for mRNA LNP Vaccines.Pharmaceutics · 2025Review
- Engineering Lipid-Polymer Nanoparticles for siRNA Delivery to Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Laminar fluid ejection device enables high yield and preservation of mRNA and SaRNA LNP formulations.Scientific reports · 2025Article
- Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Lipid nanoparticles (LNPs) are the leading technology for RNA delivery, given the success of the Pfizer/BioNTech and Moderna COVID-19 mRNA (mRNA) vaccines, and small interfering RNA (siRNA) therapies (patisiran). However, optimization of LNP process parameters and compositions for larger RNA payloads such as self-amplifying RNA (saRNA), which can have complex secondary structures, have not been carried out. Furthermore, the interactions between process parameters, critical quality attributes (CQAs), and function, such as protein expression and cellular activation, are not well understood. Here, we used two iterations of design of experiments (DoE) (definitive screening design and Box-Behnken design) to optimize saRNA formulations using the leading, FDA-approved ionizable lipids (MC3, ALC-0315, and SM-102). We observed that PEG is required to preserve the CQAs and that saRNA is more challenging to encapsulate and preserve than mRNA. We identified three formulations to minimize cellular activation, maximize cellular activation, or meet a CQA profile while maximizing protein expression. The significant parameters and design of the response surface modeling and multiple response optimization may be useful for designing formulations for a range of applications, such as vaccines or protein replacement therapies, for larger RNA cargoes.
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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.