microRNAs (miRNAs) play important roles in physiologic and pathologic regulation, but their delivery for use in therapeutic applications is challenging. Extracellular vesicles (EVs), which are being explored as drug delivery vehicles, are stable in circulation and contain miRNAs. However, using EVs to deliver miRNAs has been limited by the difficulty of loading miRNAs into EVs. In this study we describe a method to produce miRNA-enriched EVs in large quantities. We show that overexpressing an miRNA precursor in cells enormously increases the specific miRNA content in EVs. Growing cells in bioreactors can generate large quantities of miRNA-enriched EVs that can be concentrated by tangential flow filtration. The EVs thus produced can enter into cells in vitro and can increase circulating miRNA levels in vivo in animal models. These miRNA-enriched EVs may be useful in various in vitro and in vivo applications. Impact Statement This article describes a method for producing microRNA (miRNA)-enriched extracellular vesicles in large quantities. It enables in vivo delivery of specific miRNA for therapeutic applications.
基金:
Wake Forest Clinical and Translational Science Institute through NIH [UL1 TR 001420]
第一作者单位:[1]Wake Forest Univ Hlth Sci, Inst Regenerat Med, Med Ctr Blvd, Winston Salem, NC 27157 USA
通讯作者:
推荐引用方式(GB/T 7714):
Yoo Kyung Whan,Li Ning,Makani Vishruti,et al.Large-Scale Preparation of Extracellular Vesicles Enriched with Specific microRNA[J].TISSUE ENGINEERING PART C-METHODS.2018,24(11):637-644.doi:10.1089/ten.tec.2018.0249.
APA:
Yoo, Kyung Whan,Li, Ning,Makani, Vishruti,Singh, Ravi N.,Atala, Anthony&Lu, Baisong.(2018).Large-Scale Preparation of Extracellular Vesicles Enriched with Specific microRNA.TISSUE ENGINEERING PART C-METHODS,24,(11)
MLA:
Yoo, Kyung Whan,et al."Large-Scale Preparation of Extracellular Vesicles Enriched with Specific microRNA".TISSUE ENGINEERING PART C-METHODS 24..11(2018):637-644