ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Discovery of Ketal-Ester Ionizable Lipid Nanoparticle with Reduced Hepatotoxicity, Enhanced Spleen Tropism for mRNA Vaccine Delivery.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The trial behind it
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Who cites it
26 citing papers in PubMed.
- Segmented poly(A) tails with microRNA target sites confer tissue-specific regulation for mRNA therapeutics.Molecular therapy. Nucleic acids · 2026Article
- Overcoming hepatic tropism: Precision engineering of lipid nanoparticles for extrahepatic RNA delivery.Materials today. Bio · 2026Review
- Rewriting the mRNA Delivery Map: Albumin Hitchhiking Lipid Nanoparticles for Safer and Smarter Nanomedicine.ACS materials Au · 2026Review
- Spatial Tail Design in Ionizable Lipids Enhances the Safety and Efficacy of mRNA Delivery.Small methods · 2026Article
- Decoding Undesirable Inflammatory Responses of Nucleic Acid-Delivering Lipid Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Recent advances in lipid nanoparticles for cancer vaccine delivery: Challenges and future perspectives.International journal of pharmaceutics: X · 2026Review
- Thioester-Containing Ionizable Lipids with Enhanced Endosomal Escape and Biodegradability for mRNA and tRNA Delivery.Pharmaceutics · 2026Article
- Deciphering the biological fate of mRNA-LNP-based biologics: A perspective from tissue to intracellular distribution.Acta pharmaceutica Sinica. B · 2026Review
- Optimizing C14120-based LNPs forMolecular therapy. Nucleic acids · 2026Article
- A Precision-Engineered DC-Targeting mRNA-LNP Neoantigen Vaccine Elicits Stronger T Cell Responses and Exhibits Superior Tumor Control.Vaccines · 2026Article
- Advances in nano-delivery systems for overcoming the challenges of applying siRNA drugs in tumor therapy.Asian journal of pharmaceutical sciences · 2026Review
- Circular RNAs: Key Regulators of Tumor Metabolic Reprogramming and Clinical Translation.Oncology research · 2026Review
- Rational design and applications of piperazine and cyclohexane ionizable lipids for PKU and SSADH deficiency.Molecular therapy. Nucleic acids · 2025Article
- Development of a novel-ionizable-lipid-based mRNA vaccine for broad protection againstMolecular therapy. Nucleic acids · 2025Article
- Engineering Anti-Tumor Immunity: An Immunological Framework for mRNA Cancer Vaccines.Vaccines · 2025Review
- Precision Targeting of Myeloid Cells via Peptide Dendrimer-Lipid Nanocarriers: A Novel Platform for Potent Cancer Immunotherapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- mRNA Cancer Vaccines: From Pandemic Paradigm to Personalized Oncology Therapeutics.Cancer innovation · 2025Review
- Emerging lipid nanoparticle systems capable of efficient intramuscular RNA delivery.Nanomedicine (London, England) · 2025Review
- Review
- Hepatic Metabolic Dysregulation as a Potential Amplifier of Leukemogenesis Following mRNA Vaccination: A Novel Mechanistic Hypothesis.Medicina (Kaunas, Lithuania) · 2025Article
Corrections and comments
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Authors and funding
22 authors.
Funding
Abstract
The safety and efficacy of the lipid nanoparticle (LNP) delivery system are crucial for the successful development of messenger RNA vaccines. We designed and synthesized a series of ketal ester lipids (KELs), featuring a biodegradable ketal moiety in the linker and ester segments in the tail. Through iterative optimization of the head and tail groups of KELs, we tuned the pKa and molecular shapes, and identified (4S)-KEL12 as a safe and efficient ionizable lipid for mRNA delivery. (4S)-KEL12 LNP showed significantly higher delivery efficacy and lower toxicity than the DLin-MC3-DMA LNP. In comparison to SM-102 LNP, (4S)-KEL12 LNP exhibited better spleen tropism, reduced liver tropism, and hepatotoxicity. Additionally, (4S)-KEL12 demonstrated good biodegradability following intramuscular or intravenous injection. Notably, (4S)-KEL12 LNP encapsulated with a therapeutic mRNA cancer vaccine elicited robust cellular immune responses leading to substantial tumor regression along with prolonged survival in tumor-bearing mice. Our results suggest that (4S)-KEL12 LNP holds great promise for mRNA vaccine delivery. The comprehensive analysis of the structure-activity relationship, toxicity, biodegradability, distribution, expression, efficacy, and stereochemistry of these LNPs will greatly contribute to the rational design and discovery of novel lipid-based delivery systems.
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