ArticleNature chemistry2024
Fast and facile synthesis of amidine-incorporated degradable lipids for versatile mRNA delivery in vivo.
Article in Nature chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Who cites it
29 citing papers in PubMed.
- Structural evolution of ionizable lipids for nucleic acid delivery.Nature reviews. Chemistry · 2026Review
- Bioactive lipid-derived nanoparticles for RNA delivery.Materials today (Kidlington, England) · 2026Article
- Ligand-Mediated Reprogramming Redirects Liver-Tropic Ionizable Lipid Nanoparticles for Lung-Selective mRNA Delivery.Angewandte Chemie (International ed. in English) · 2026Article
- Lipoic Acid Derivative/PEI Composite Nanoparticles Enable Efficient mRNA Delivery via Thiol-Mediated Cellular Uptake.Macromolecular bioscience · 2026Article
- Antioxidant lipid nanoparticles enhance mRNA stability for regeneration therapy and gene editing.Nature communications · 2026Article
- The RNA delivery dilemma-lipid versus polymer nanoparticle platforms.Drug delivery and translational research · 2026Article
- β-Triketone-Based Ionizable Cationic Lipids Synthesized via Click Chemistry for siRNA Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Boosting ribosomal translationBioactive materials · 2026Article
- Emerging Non-Conventional Approaches in mRNA-LNP Formulation for Therapeutic Applications.Pharmaceutics · 2026Review
- Thioester-Containing Ionizable Lipids with Enhanced Endosomal Escape and Biodegradability for mRNA and tRNA Delivery.Pharmaceutics · 2026Article
- Artificial intelligence-guided design of LNPs for in vivo targeted mRNA delivery via analysis of the spatial conformation of ionizable lipids.Nature biomedical engineering · 2026Article
- A worm-like nucleic acid nanostructure for gene delivery and endosomal escape via ClC3 ion exchanger.Science advances · 2026Article
- Accelerate the Highly Efficient Development of mRNA Vaccines Through Advanced Computational Methods.MedComm · 2026Review
- Engineered internal architecture of core-shell lipid nanoparticles promotes efficient mRNA endosomal release.Nature communications · 2026Article
- Biomimetic liposomes in drug delivery: from design mechanisms to applications.Chemical Society reviews · 2026Review
- Lipid Nanoparticles for Delivery of CRISPR Gene Editing Components.Small methods · 2026Review
- Tissue-specific mRNA delivery and prime editing with peptide-ionizable lipid nanoparticles.Nature materials · 2026Article
- High-Throughput Strategies for Streamlining Lipid Nanoparticle Development Pipeline.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Recent Advances and Future Prospects in Biological-Membrane-Targeted Polymers.Polymer science & technology (Washington, D.C.) · 2025Review
- Circular RNA lipid nanoparticle vaccine against SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Lipid nanoparticles (LNPs) are widely used for mRNA delivery, with cationic lipids greatly affecting biodistribution, cellular uptake, endosomal escape and transfection efficiency. However, the laborious synthesis of cationic lipids limits the discovery of efficacious candidates and slows down scale-up manufacturing. Here we develop a one-pot, tandem multi-component reaction based on the rationally designed amine-thiol-acrylate conjugation, which enables fast (1 h) and facile room-temperature synthesis of amidine-incorporated degradable (AID) lipids. Structure-activity relationship analysis of a combinatorial library of 100 chemically diverse AID-lipids leads to the identification of a tail-like amine-ring-alkyl aniline that generally affords efficacious lipids. Experimental and theoretical studies show that the embedded bulky benzene ring can enhance endosomal escape and mRNA delivery by enabling the lipid to adopt a more conical shape. The lead AID-lipid can not only mediate local delivery of mRNA vaccines and systemic delivery of mRNA therapeutics, but can also alter the tropism of liver-tropic LNPs to selectively deliver gene editors to the lung and mRNA vaccines to the spleen.
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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.