Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson's disease treatment.
Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson's disease treatment.
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DOI：
10.1038/s41467-018-03733-8
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发表时间：
2018-04-03
影响因子：
16.6
通讯作者：
Fussenegger M
中科院分区：
文献类型：
--
作者：
Kojima R;Bojar D;Rizzi G;Hamri GC;El-Baba MD;Saxena P;Ausländer S;Tan KR;Fussenegger M
外来体是细胞衍生的纳米囊泡（50-150 nm），其介导细胞间通讯，并且是候选治疗剂。然而，外泌体信息传递（如mRNA）的效率低下以及缺乏创建设计外泌体的方法阻碍了它们发展为治疗性干预措施。在这里，我们报告了一组外泌体转移到细胞（EXOtic）装置，其能够在工程化哺乳动物细胞中高效、可定制地生产设计者外泌体。外泌体生产细胞中的这些遗传编码的装置增强外泌体生产、特异性mRNA包装和将mRNA递送到靶细胞的胞质溶胶中，使得能够进行有效的细胞间通讯而不需要浓缩外泌体。此外，植入活体小鼠中的工程生产细胞可以始终如一地将货物mRNA递送到大脑。通过设计者外泌体的治疗性过氧化氢酶mRNA递送在帕金森病的体外和体内模型中减弱了神经毒性和神经炎症，表明EXOtic装置对于基于RNA递送的治疗应用的潜在有用性。外泌体作为细胞间信息传递器发挥作用，并且是用于递送治疗剂的候选物。在这里，作者介绍了EXOtic，一种用于原位生产设计外泌体的合成生物学装置，并展示了在帕金森病模型中的体内应用。
Exosomes are cell-derived nanovesicles (50–150 nm), which mediate intercellular communication, and are candidate therapeutic agents. However, inefficiency of exosomal message transfer, such as mRNA, and lack of methods to create designer exosomes have hampered their development into therapeutic interventions. Here, we report a set of EXOsomal transfer into cells (EXOtic) devices that enable efficient, customizable production of designer exosomes in engineered mammalian cells. These genetically encoded devices in exosome producer cells enhance exosome production, specific mRNA packaging, and delivery of the mRNA into the cytosol of target cells, enabling efficient cell-to-cell communication without the need to concentrate exosomes. Further, engineered producer cells implanted in living mice could consistently deliver cargo mRNA to the brain. Therapeutic catalase mRNA delivery by designer exosomes attenuated neurotoxicity and neuroinflammation in in vitro and in vivo models of Parkinson’s disease, indicating the potential usefulness of the EXOtic devices for RNA delivery-based therapeutic applications. Exosomes function as intercellular information transmitters and are candidates for delivery of therapeutic agents. Here the authors present EXOtic, a synthetic biology device for in-situ production of designer exosomes and demonstrate in vivo application in models of Parkinson's disease.
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影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
DOI：
10.1016/j.apsb.2016.02.001
发表时间：
2016-07
期刊：
Acta pharmaceutica Sinica. B
影响因子：
--
作者：
Ha D;Yang N;Nadithe V
通讯作者：
Nadithe V
外泌体作为帕金森氏病疗法的药物。
DOI：
10.1016/j.jconrel.2015.03.033
发表时间：
2015-06-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Haney MJ;Klyachko NL;Zhao Y;Gupta R;Plotnikova EG;He Z;Patel T;Piroyan A;Sokolsky M;Kabanov AV;Batrakova EV
通讯作者：
Batrakova EV
影响因子：
15.1
作者：
Bernstein AI;Garrison SP;Zambetti GP;O'Malley KL
通讯作者：
O'Malley KL
DOI：
10.4061/2011/436813
发表时间：
2011-02-22
期刊：
Parkinson's disease
影响因子：
--
作者：
Ferrari CC;Tarelli R
通讯作者：
Tarelli R