Delivery of Therapeutic Proteins via Extracellular Vesicles: Review and Potential Treatments for Parkinson’s Disease, Glioma, and Schwannoma

被引:0
作者
Justin Hall
Shilpa Prabhakar
Leonora Balaj
Charles P. Lai
Richard A. Cerione
Xandra O. Breakefield
机构
[1] Cornell University,Departments of Chemistry and Chemical Biology and Molecular Medicine
[2] Harvard Medical School,Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and NeuroDiscovery Center
[3] National Tsing Hua University,Institute of Biomedical Engineering
[4] Massachusetts General Hospital-East,Molecular Neurogenetics Unit
来源
Cellular and Molecular Neurobiology | 2016年 / 36卷
关键词
Exosomes; Extracellular vesicles; Parkinson’s disease; Glioma; Schwannoma; Therapeutic protein delivery;
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摘要
Extracellular vesicles present an attractive delivery vehicle for therapeutic proteins. They intrinsically contain many proteins which can provide information to other cells. Advantages include reduced immune reactivity, especially if derived from the same host, stability in biologic fluids, and ability to target uptake. Those from mesenchymal stem cells appear to be intrinsically therapeutic, while those from cancer cells promote tumor progression. Therapeutic proteins can be loaded into vesicles by overexpression in the donor cell, with oligomerization and membrane sequences increasing their loading. Examples of protein delivery for therapeutic benefit in pre-clinical models include delivery of: catalase for Parkinson’s disease to reduce oxidative stress and thus help neurons to survive; prodrug activating enzymes which can convert a prodrug which crosses the blood–brain barrier into a toxic chemotherapeutic drug for schwannomas and gliomas; and the apoptosis-inducing enzyme, caspase-1 under a Schwann cell specific promoter for schwannoma. This therapeutic delivery strategy is novel and being explored for a number of diseases.
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页码:417 / 427
页数:10
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