ArticleProceedings of the National Academy of Sciences of the United States of America2025
Glycolipid nanoparticles target the spleen and detarget the liver without charge.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
9 citing papers in PubMed.
- Delivering the blueprint: Advances and challenges in mRNA therapeutics for the respiratory system.International journal of pharmaceutics: X · 2026Review
- Bioactive lipid-derived nanoparticles for RNA delivery.Materials today (Kidlington, England) · 2026Article
- Chimeric IL-6/4R-LL37 Engineered Macrophages Achieve Synchronized Inflammation Control and Antimicrobial Defence in Sepsis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Solid-Phase Glycolipid Synthesis Expedites Liposome Functionalization.Journal of the American Chemical Society · 2026Article
- In Vivo mRNA-Lipid Nanoparticle CAR-T Cell Engineering: Advances, Challenges, and Clinical Translation.Biomedicines · 2026Review
- Gene therapy for liver diseases: methods, challenges and opportunities.Journal of nanobiotechnology · 2026Review
- Recent Developments in Lipid Nanoparticle-Mediated Delivery of Biotherapeutics and Gene Therapy Across the Blood-Brain Barrier.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Artificial intelligence empowered biomaterials for cancer therapy: From rational design to clinical translation.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2026Article
- Nanovaccines in gastrointestinal cancers.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Lipid nanoparticles (LNPs) formulated with a neutral helper lipid can deliver RNA to the liver in humans. However, clinically relevant delivery to other tissues has remained challenging. To avoid the liver, scientists often add antibodies or helper lipids with a permanent charge. Here, we report an alternative approach: antibody- and charge-independent liver detargeting. Using DNA barcoding to test 109 chemically distinct LNPs in vivo, we found that replacing a neutral helper lipid with a neutral glycolipid reduced liver delivery and increased splenic delivery. Consistent with this differential tropism, these glycolipid nanoparticles caused differences in downstream cellular signaling in vivo compared to traditional LNPs. These data suggest that extrahepatic LNPs can be designed without the imposition of a net negative or positive charge.
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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.