ArticleJournal of controlled release : official journal of the Controlled Release Society2023
Substituting racemic ionizable lipids with stereopure ionizable lipids can increase mRNA delivery.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 44 citations in OpenAlex.
- mRNA lipid nanoparticle vaccines: current status, challenges and future prospects.Molecular biomedicine · 2026Review
- Copper-Catalyzed Amino Radical Transfer-Mediated Deborylation for Chiral Ester Synthesis.Angewandte Chemie (International ed. in English) · 2026Article
- Induction of mucosal immune responses against SARS-CoV-2: a heterologous intramuscular mRNA-LNP prime/pulmonary recombinant subunit pull vaccination strategy.Scientific reports · 2026Article
- Deciphering the biological fate of mRNA-LNP-based biologics: A perspective from tissue to intracellular distribution.Acta pharmaceutica Sinica. B · 2026Review
- Lipid nanoparticle GM-CSF replacement for autoimmune pulmonary alveolar proteinosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Possible Ways of Reducing Adverse Events Associated with mRNA Vaccines Encapsulated in Lipid Nanoparticles.Bulletin of experimental biology and medicine · 2026Review
- Design of cationic ionizable lipids for the delivery of therapeutic nucleic acids.Molecular therapy. Methods & clinical development · 2025Review
- mRNA therapeutics: Transforming medicine through innovation in design, delivery, and disease treatment.Molecular therapy. Nucleic acids · 2025Review
- Nanoparticle delivery of a prodrug-activating bacterial enzyme leads to anti-tumor responses.Nature communications · 2025Article
- Chemistry, manufacturing and controls strategies for using novel excipients in lipid nanoparticles.Nature nanotechnology · 2025Review
- Lipid nanoparticle-mediated RNA delivery for immune cell modulation.European journal of immunology · 2024Review
- Enhancing RNA-lipid nanoparticle delivery: Organ- and cell-specificity and barcoding strategies.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
- Breaking the final barrier: Evolution of cationic and ionizable lipid structure in lipid nanoparticles to escape the endosome.Advanced drug delivery reviews · 2024Review
- Review
- Smart delivery vehicles for cancer: categories, unique roles and therapeutic strategies.Nanoscale advances · 2024Review
- Isoprenoid CARTs:Biomacromolecules · 2024Article
- Leveraging high-throughput screening technologies in targeted mRNA delivery.Materials today. Bio · 2024Review
- Lymph node macrophages drive innate immune responses to enhance the anti-tumor efficacy of mRNA vaccines.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Lipid Nanoparticle (LNP) Delivery Carrier-Assisted Targeted Controlled Release mRNA Vaccines in Tumor Immunity.Vaccines · 2024Review
- mRNA vaccines and their delivery strategies: A journey from infectious diseases to cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Lipid nanoparticles (LNPs) have delivered siRNA and mRNA drugs in humans, underscoring the potential impact of improving the therapeutic window of next-generation LNPs. To increase the LNP therapeutic window, we applied lessons from small-molecule chemistry to ionizable lipid design. Specifically, given that stereochemistry often influences small-molecule safety and pharmacokinetics, we hypothesized that the stereochemistry of lipids within an LNP would influence mRNA delivery. We tested this hypothesis in vivo using 128 novel LNPs that included stereopure derivatives of C12-200, an ionizable lipid that when formulated into LNPs delivers RNA in mice and non-human primates but is not used clinically due to its poor tolerability. We found that a novel C12-200-S LNP delivered up to 2.8-fold and 6.1-fold more mRNA in vivo than its racemic and C12-200-R controls, respectively. To identify the potential causes leading to increased delivery, we quantified LNP biophysical traits and concluded that these did not change with stereochemistry. Instead, we found that stereopure LNPs were better tolerated than racemic LNPs in vivo. These data suggest that LNP-mediated mRNA delivery can be improved by designing LNPs to include stereopure ionizable lipids.
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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.