ArticleProceedings of the National Academy of Sciences of the United States of America2024
Thiophene-based lipids for mRNA delivery to pulmonary and retinal tissues.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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
25 citing papers in PubMed, 43 citations in OpenAlex.
- Bioactive lipid-derived nanoparticles for RNA delivery.Materials today (Kidlington, England) · 2026Article
- Structural evolution of ionizable lipids for nucleic acid delivery.Nature reviews. Chemistry · 2026Review
- Lipid nanoparticles enable mRNA delivery to diverse cell types of the inner Retina.Molecular therapy. Nucleic acids · 2026Article
- Hydrophobic Tail and Linker Diversification of PEG-Lipids Unlocks Precise Muscle Tropism of mRNA-Lipid Nanoparticles.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- A novel machine learning framework-based rapid screening of ionizable lipids in LNPs for highly-efficient mRNA expression.Acta pharmaceutica Sinica. B · 2026Article
- Post-loading ribonucleic acid into lipid nanoparticle carriers.bioRxiv : the preprint server for biology · 2026Article
- Strategic lipid nanoparticle design dictates retinal delivery post inner limiting membrane disruption.Drug delivery and translational research · 2026Article
- Emerging Non-Conventional Approaches in mRNA-LNP Formulation for Therapeutic Applications.Pharmaceutics · 2026Review
- In vivo endosomal escape assay identifies mechanisms for efficient hepatic LNP delivery.Nature biotechnology · 2026Article
- High-Throughput In Vivo Screening Using Barcoded mRNA Identifies Lipid Nanoparticles With Extrahepatic Tropism for In Situ Immunoengineering.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Targeting Ocular Tissue through Surface-Modified and Multifunctional Biomaterials and mRNA-Based Therapeutics.Current pharmaceutical design · 2026Review
- Impact of PEGylation and hyaluronan functionalization on lipoplex-mediated mRNA delivery to the canine retina.Drug delivery · 2025Article
- Targeted delivery ofActa pharmaceutica Sinica. B · 2025Article
- Customizable Polymeric Nanoparticle Materials Optimized on Hypoxic Cells Facilitate mRNA Expression in the Lungs In Vivo.Advanced healthcare materials · 2025Article
- Nanoparticle-Based Pulmonary Immune Engineering.Annual review of chemical and biomolecular engineering · 2025Review
- Lung-Specific mRNA Delivery by Ionizable Lipids with Defined Structure-Function Relationship and Unique Protein Corona Feature.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Rational design and modular synthesis of biodegradable ionizable lipids via the Passerini reaction for mRNA delivery.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Preformed Vesicle Approach to LNP Manufacturing Enhances Retinal mRNA Delivery.Small (Weinheim an der Bergstrasse, Germany) · 2024Article
- Exploring the potential of cell-derived vesicles for transient delivery of gene editing payloads.Advanced drug delivery reviews · 2024Review
- A Lung-Expressing mRNA Delivery Platform with Tunable Activity in Hypoxic Environments.Journal of the American Chemical Society · 2024Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
Lipid nanoparticles (LNPs) largely rely on ionizable lipids to yield successful nucleic acid delivery via electrostatic disruption of the endosomal membrane. Here, we report the identification and evaluation of ionizable lipids containing a thiophene moiety (Thio-lipids). The Thio-lipids can be readily synthesized via the Gewald reaction, allowing for modular lipid design with functional constituents at various positions of the thiophene ring. Through the rational design of ionizable lipid structure, we prepared 47 Thio-lipids and identified some structural criteria required in Thio-lipids for efficient mRNA (messenger RNA) encapsulation and delivery in vitro and in vivo. Notably, none of the tested lipids have a pH-response profile like traditional ionizable lipids, potentially due to the electron delocalization in the thiophene core. Placement of the tails and localization of the ionizable headgroup in the thiophene core can endow the nanoparticles with the capability to reach various tissues. Using high-throughput formulation and barcoding techniques, we optimized the formulations to select two top 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.