ArticleStem cell research & therapy2024
Genetically engineered human induced pluripotent stem cells for the production of brain-targeting extracellular vesicles.
Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Advances in Extracellular Vesicle-Based Innovative Drugs Targeting Alzheimer's Disease.Molecular neurobiology · 2026Review
- Review
- The Dual Role of Glial Extracellular Vesicles in Neurodegeneration: Insights from iPSC-Based Models.International journal of molecular sciences · 2026Review
- Extracellular vesicles as therapeutic agents for retinal ganglion cell degeneration: current challenges and future prospects.International ophthalmology · 2026Review
- Review
- EV-Encapsulated Mitochondrial miRNAs: Enhancing Cardiomyocyte Bioenergetics.International journal of molecular sciences · 2026Review
- The Jekyll and Hyde of Extracellular Vesicles: Dual Roles as Disease Drivers and Therapeutic Saviors in Diabetic Brain.Molecular neurobiology · 2026Review
- Bioengineering of extracellular vesicles with scaffold proteins for drug delivery.Journal of nanobiotechnology · 2026Review
- Engineered Exosomal miRNAs for Post-Stroke Neural Repair: Mechanisms, Delivery Strategies, and Translational Challenges.International journal of nanomedicine · 2026Review
- Genetically platform presenting CD24 ScFv enhance antitumor immunity by restoring macrophage phagocytosis and modulating the immune environment.Cell communication and signaling : CCS · 2025Article
- Generation of Cellular Biofactories for Scalable Production of Surface-Engineered Extracellular Vesicles via CRISPR Genome Editing.bioRxiv : the preprint server for biology · 2025Article
- Engineered Extracellular Vesicles for Targeted Paclitaxel Delivery in Cancer Therapy: Advances, Challenges, and Prospects.Cellular and molecular bioengineering · 2025Review
- Review
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9 authors.
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Abstract
backgroundExtracellular vesicles (EVs) are cell-secreted membrane vesicles that have become a promising, natural nanoparticle system for delivering either naturally carried or exogenously loaded therapeutic molecules. Among reported cell sources for EV manufacture, human induced pluripotent stem cells (hiPSCs) offer numerous advantages. However, hiPSC-EVs only have a moderate ability for brain delivery. Herein, we sought to develop a stable hiPSC line for producing EVs with substantially enhanced brain targeting by genetic engineering to overexpress rabies viral glycoprotein (RVG) peptide fused to the N terminus of lysosomal associated membrane protein 2B (RVG-Lamp2B) which has been shown capable of boosting the brain delivery of EVs via the nicotinic acetylcholine receptor.
methodsAn RVG-Lamp2B-HA expression cassette was knocked into the AAVS1 safe harbor locus of a control hiPSC line using the CRISPR/Cas9-assisted homologous recombination. Western blot was used to detect the expression of RVG-Lamp2B-HA in RVG-edited hiPSCs as well as EVs derived from RVG-edited hiPSCs. Uptake of EVs by SH-SY5Y cells in the presence of various endocytic inhibitors was analyzed using flow cytometry. Biodistribution and brain delivery of intravenously injected control and RVG-modified EVs in wild-type mice were examined using ex vivo fluorescent imaging.
resultsHere we report that an RVG-Lamp2B-HA expression cassette was knocked into the AAVS1 safe harbor locus of a control hiPSC line using the CRISPR/Cas9-assisted homologous recombination. The RVG-edited iPSCs have normal karyotype, express pluripotency markers, and have differentiation potential. Expression of RVG-Lamp2B-HA was detected in total cell extracts as well as EVs derived from RVG-edited (vs. control) hiPSCs. The RVG-modified EVs enter neuronal cells via distinct endocytic pathways, compared with control EVs. The biodistribution study confirmed that EVs derived from RVG-edited hiPSCs possess higher brain delivery efficiency.
conclusionTaken together, we have established stable, genetically engineered hiPSCs for producing EVs with RVG expression, offering the improved ability for brain-targeted drug delivery.
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