ArticleCell reports. Medicine2025
Cardiolipin-mimic lipid nanoparticles without antibody modification delivered senolytic in vivo CAR-T therapy for inflamm-aging.
Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed.
- Targeted delivery of mRNA to immune cells forDrug delivery · 2026Review
- Human T cell engineering via serial delivery of mRNA encapsulated within lipid nanoparticles.Molecular therapy. Nucleic acids · 2026Article
- Delivering the blueprint: Advances and challenges in mRNA therapeutics for the respiratory system.International journal of pharmaceutics: X · 2026Review
- Targeting the CD4Molecular biomedicine · 2026Article
- Structural evolution of ionizable lipids for nucleic acid delivery.Nature reviews. Chemistry · 2026Review
- Rewiring immunity with in vivo CAR T cell engineering.Nature cancer · 2026Review
- Review
- Immune surveillance and immune evasion of senescent cells.Nature reviews. Immunology · 2026Review
- Advancements in delivery systems for in vivo chimeric antigen receptor T-cell therapy in urological diseases.Current urology · 2026Review
- Advances in skin aging: integrating epigenetic, cellular, and immune mechanisms for targeted therapy.Immunity & ageing : I & A · 2026Review
- A Time-Resolved In Situ SAXS Method for Real-Time Monitoring of Lipid Nanoparticles Assembly.Membranes · 2026Article
- Decoding the functional network of circular RNAs encoding proteins in hepatocellular carcinoma: from carcinogenesis to clinical transformation.Journal of advanced research · 2026Review
- Nanotechnology-enhanced CAR-T therapy strategies in cancer, aging, and autoimmune diseases.Journal of hematology & oncology · 2026Review
- In Vivo T-Cell Engineering: Revolution in Delivery Strategies and Clinical Translation.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Functionalized Lipid Nanoparticles for Targeted RNA Delivery in Immune and Inflammatory Diseases.Biomedicines · 2026Review
- In vivo CAR-cell therapy: current challenges and emerging therapeutic advances.Molecular biomedicine · 2026Review
- Review
- T cell-inspired therapeutic delivery platforms: From nanomedicines to cell therapy.Materials today. Bio · 2026Review
- Circular RNAs in cancer: Its biogenesis, functions, relationships with cancer progression, applications in immunotherapy and biomarker potentials.Cancer immunology, immunotherapy : CII · 2026Review
- Cancer and aging: complex associations and therapeutic targets.Molecular biomedicine · 2026Review
Corrections and comments
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Authors and funding
24 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
mRNA-based in vivo chimeric antigen receptor (CAR)-T cell engineering offers advantages over ex vivo therapies, including streamlined manufacturing and transient expression. However, current delivery methods require antibody-modified vehicles with manufacturing challenges. In this study, inspired by cardiolipin, we identify cardiolipin-like di-phosphoramide lipids that improve T cell transfection without targeting ligands, both in vitro and in vivo. The T cell-favored tropism is likely due to the lipid's packing, shape, and rigidity. Encapsulating circular RNA further prolongs mRNA expression in the spleen and T cells. Using PL40 lipid nanoparticles, we deliver mRNA encoding a CAR targeting the senolytic and inflammatory antigen urokinase-type plasminogen activator receptor (uPAR), alleviating uPAR-related liver fibrosis and rheumatoid arthritis (RA). Single-cell sequencing in humans confirms uPAR's relevance to senescence and inflammation in RA. To facilitate clinical translation, we screen and humanize single-chain variable fragments (scFvs) against uPAR, establishing a PL40 mRNA-encoded humanized uPAR CAR with potential for treating aging-inflamed disorders.
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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.