ArticleNature materials2024
Accelerating ionizable lipid discovery for mRNA delivery using machine learning and combinatorial chemistry.
Article in Nature materials, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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The trial behind it
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Who cites it
111 citing papers in PubMed.
- From RNA design to delivery: Computational strategies for functional RNA therapeutics.Bioactive materials · 2027Review
- Cas12a chRDNA-mediatedMolecular therapy. Nucleic acids · 2026Article
- Structural evolution of ionizable lipids for nucleic acid delivery.Nature reviews. Chemistry · 2026Review
- Combinatorial synthesis of novel polycations for mRNA deliveryRSC applied polymers · 2026Article
- mRNA lipid nanoparticle vaccines: current status, challenges and future prospects.Molecular biomedicine · 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
- Codon-optimizedMolecular therapy. Nucleic acids · 2026Article
- Engineering mRNA-LNP Medicines for the Ageing Brain: Opportunities and Challenges for Neurodegenerative Diseases.Exploration (Beijing, China) · 2026Review
- Skin Relevant Biomaterials from Wound Healing, Medical Aesthetics, Flexible Electronics to Artificial Intelligence and Beyond.Advanced materials (Deerfield Beach, Fla.) · 2026Review
- Hydrophobic Tail and Linker Diversification of PEG-Lipids Unlocks Precise Muscle Tropism of mRNA-Lipid Nanoparticles.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Review
- Precision chemical engineering of dendrimers for nucleic acid delivery.Nature reviews. Chemistry · 2026Review
- Preparation of placenta-tropic mRNA lipid nanoparticles for pregnancy disorders.Nature protocols · 2026Review
- Critical chemistry manufacturing and controls considerations for mRNA lipid nanoparticle translation.Discover nano · 2026Review
- Lipid Nanoparticles for Gene Therapy: Unresolved Challenges in Manufacturing, Transdermal Delivery, Machine Learning, Endosomal Escape, and the Protein Corona.Pharmaceutics · 2026Review
- A novel machine learning framework-based rapid screening of ionizable lipids in LNPs for highly-efficient mRNA expression.Acta pharmaceutica Sinica. B · 2026Article
- Delivering the future of immunotherapy: A state-of-the-art review of gene editing in immune cells with lipid nanoparticles.Materials today. Bio · 2026Review
- Living Inorganic Nanomaterials: Design, Preparation, and Biomedical Applications.Advanced materials (Deerfield Beach, Fla.) · 2026Review
- Personalized cancer vaccines: bridging immune-oncology and precision medicine for advanced therapeutics.Signal transduction and targeted therapy · 2026Review
- AI meets high-throughput screening of LNPs.Nature biomedical engineering · 2026Article
51 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
To unlock the full promise of messenger (mRNA) therapies, expanding the toolkit of lipid nanoparticles is paramount. However, a pivotal component of lipid nanoparticle development that remains a bottleneck is identifying new ionizable lipids. Here we describe an accelerated approach to discovering effective ionizable lipids for mRNA delivery that combines machine learning with advanced combinatorial chemistry tools. Starting from a simple four-component reaction platform, we create a chemically diverse library of 584 ionizable lipids. We screen the mRNA transfection potencies of lipid nanoparticles containing those lipids and use the data as a foundational dataset for training various machine learning models. We choose the best-performing model to probe an expansive virtual library of 40,000 lipids, synthesizing and experimentally evaluating the top 16 lipids flagged. We identify lipid 119-23, which outperforms established benchmark lipids in transfecting muscle and immune cells in several tissues. This approach facilitates the creation and evaluation of versatile ionizable lipid libraries, advancing the formulation of lipid nanoparticles for precise mRNA delivery.
Indexed as
Identifiers
38740955What OpenQuestion holds
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.