ArticleTranslational neurodegeneration2025
Development of human targeted extracellular vesicles loaded with shRNA minicircles to prevent parkinsonian pathology.
Article in Translational neurodegeneration, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Regenerative strategies for ALS: stem cells and extracellular vesicles.Discover nano · 2026Review
- Extracellular vesicle-mediated bidirectional communication between the brain and peripheral organs in Alzheimer's disease: evidence, mechanisms, and translational perspectives.Journal of nanobiotechnology · 2026Review
- Angiopep-2-engineered extracellular vesicles derived from spinal cord injury-responsive brown adipose tissue for targeted neuroinflammation modulation.Journal of nanobiotechnology · 2026Article
- Genomic characterization of rabies virus glycoprotein co-expressing CD70 CAR-T cells during killing of glioma cellsFrontiers in immunology · 2026Article
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16 authors.
Funding
Abstract
backgroundNeurological disorders are the second leading cause of death and the leading cause of disability in the world. Thus, the development of novel disease-modifying strategies is clearly warranted. We have previously developed a therapeutic approach using mouse targeted rabies virus glycoprotein (RVG) extracellular vesicles (EVs) to deliver minicircles (MCs) expressing shRNA (shRNA-MCs) to induce long-term α-synuclein down-regulation. Although the previous therapy successfully reduced the pathology, the clinical translation was extremely unlikely since they were mouse extracellular vesicles.
methodsTo overcome this limitation, we developed a source of human RVG-EVs compatible with a personalized therapy using immature dendritic cells. Human peripheral blood monocytes were differentiated in vitro into immature dendritic cells, which were transfected to express the RVG peptide. RVG-EVs containing shRNA-MCs, loaded by electroporation, were injected intravenously in the α-synuclein performed fibril (PFF) mouse model. Level of α-synuclein, phosphorylated α-synuclein aggregates, dopaminergic neurons and motor function were evaluated 90 days after the treatment. To confirm that EVs derived from patients were suitable as a vehicle, proteomic analysis of EVs derived from control, initial and advanced Parkinson's disease was performed.
resultsThe shRNA-MCs could be successfully loaded into human RVG-EVs and downregulate α-synuclein in SH-SY5Y cells. Intravenous injection of the shRNA-MC-loaded RVG-EVs induced long-term downregulation of α-synuclein mRNA expression and protein level, decreased α-synuclein aggregates, prevented dopaminergic cell death and ameliorated motor impairment in the α-synuclein PFF mouse model. Moreover, we confirmed that the EVs from PD patients are suitable as a personalized therapeutic vehicle.
conclusionOur study confirmed the therapeutic potential of shRNA-MCs delivered by human RVG-EVs for long-term treatment of neurodegenerative diseases. These results pave the way for clinical use of this approach.
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