ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
Lipid Nanoparticles Deliver the Therapeutic VEGFA mRNA In Vitro and In Vivo and Transform Extracellular Vesicles for Their Functional Extensions.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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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
51 citing papers in PubMed, 80 citations in OpenAlex.
- Rewriting the mRNA Delivery Map: Albumin Hitchhiking Lipid Nanoparticles for Safer and Smarter Nanomedicine.ACS materials Au · 2026Review
- Vectored Immunoprophylaxis for Mucosal Immunity: Advances and Challenges Associated with Recombinant Secretory IgA Expression.Vaccines · 2026Review
- Extracellular Vesicles in Cancer: Biomarkers, Mechanisms, and Emerging Diagnostic Technologies.Advanced healthcare materials · 2026Review
- Decoding Undesirable Inflammatory Responses of Nucleic Acid-Delivering Lipid Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Spatio-temporal targeting of cardiac cells with lipid nanoparticles after myocardial infarction.Journal of molecular and cellular cardiology plus · 2026Article
- In vivo CAR-M therapy: advancing precision delivery and programmable immune remodeling.Cell communication and signaling : CCS · 2026Review
- Targeted Delivery of mRNA to the Heart via Extracellular Vesicles or Lipid Nanoparticles.Journal of extracellular vesicles · 2026Article
- Endogenous Engineering Reprograms Extracellular Vesicles for Enhanced Therapeutic Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- CAR-CD34 (+) hematopoietic stem/progenitor cells produced in vivo protect against thoracic aortic aneurysm and dissection.Nature communications · 2026Article
- The Status of Extracellular Vesicles as Drug Carriers and Therapeutics.Nature reviews bioengineering · 2026Article
- Regenerative Approach for Improving Flap Survival: Perspective of Angiogenesis.Biomimetics (Basel, Switzerland) · 2026Review
- Extracellular Vesicles in Liver Fibrosis: Pathogenic Messengers, Diagnostic Biomarkers, and Therapeutic Nanovectors.Pharmaceutics · 2026Review
- The evolution of lipid nanoparticles: Paving the way for next-generation nucleic acid medicines.Asian journal of pharmaceutical sciences · 2026Review
- The mRNA-Based Innovative Strategy: Progress and Challenges.Nano-micro letters · 2026Review
- Precision Engineering of Extracellular Vesicles as Programmable Carriers for mRNA Therapeutics.International journal of nanomedicine · 2026Review
- A Systematic Review of Advanced Drug Delivery Systems: Engineering Strategies, Barrier Penetration, and Clinical Progress (2016-April 2025).Pharmaceutics · 2025Review
- Extracellular Vesicles in Calcific Aortic Valve Disease: From Biomarkers to Drug Delivery Applications.Biomolecules · 2025Review
- Histidine Decapeptide-Incorporating Lipid Nanoparticles with Low Ionizable Lipids Proportion for Efficient Small Interfering RNA Delivery.Macromolecular bioscience · 2025Article
- Extracellular Vesicles Released by Bovine Alphaherpesvirus 1-Infected A549 Cells May Limit Subsequent Infections of the Progeny Virus.International journal of molecular sciences · 2025Article
- Nanoparticle-Based Pulmonary Immune Engineering.Annual review of chemical and biomolecular engineering · 2025Review
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 2 countries.
Funding
Abstract
Lipid nanoparticles (LNPs) are currently used to transport functional mRNAs, such as COVID-19 mRNA vaccines. The delivery of angiogenic molecules, such as therapeutic VEGF-A mRNA, to ischemic tissues for producing new blood vessels is an emerging strategy for the treatment of cardiovascular diseases. Here, the authors deliver VEGF-A mRNA via LNPs and study stoichiometric quantification of their uptake kinetics and how the transport of exogenous LNP-mRNAs between cells is functionally extended by cells' own vehicles called extracellular vesicles (EVs). The results show that cellular uptake of LNPs and their mRNA molecules occurs quickly, and that the translation of exogenously delivered mRNA begins immediately. Following the VEGF-A mRNA delivery to cells via LNPs, a fraction of internalized VEGF-A mRNA is secreted via EVs. The overexpressed VEGF-A mRNA is detected in EVs secreted from three different cell types. Additionally, RNA-Seq analysis reveals that as cells' response to LNP-VEGF-A mRNA treatment, several overexpressed proangiogenic transcripts are packaged into EVs. EVs are further deployed to deliver VEGF-A mRNA in vitro and in vivo. Upon equal amount of VEGF-A mRNA delivery via three EV types or LNPs in vitro, EVs from cardiac progenitor cells are the most efficient in promoting angiogenesis per amount of VEGF-A protein produced. Intravenous administration of luciferase mRNA shows that EVs could distribute translatable mRNA to different organs with the highest amounts of luciferase detected in the liver. Direct injections of VEGF-A mRNA (via EVs or LNPs) into mice heart result in locally produced VEGF-A protein without spillover to liver and circulation. In addition, EVs from cardiac progenitor cells cause minimal production of inflammatory cytokines in cardiac tissue compared with all other treatment types. Collectively, the data demonstrate that LNPs transform EVs as functional extensions to distribute therapeutic mRNA between cells, where EVs deliver this mRNA differently than LNPs.
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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.