Selective Encapsulation of Therapeutic mRNA in Engineered Extracellular Vesicles by DNA Aptamer.

Abstract

Extracellular vesicles (EV)-based delivery of therapeutic mRNAs is challenged by the low loading efficiency. In this study, we designed a DNA aptamer consisting of two parts: the single strand part recognized the AUG region of target mRNA, preventing mRNA from translation and ribosome assembly; and the double strand part containing the elements recognized by the CD9-ZF (zinc finger) motifs, sorting DNA aptamer-mRNA complex into CD9-ZF engineered EVs. <i>In vitro</i> and <i>in vivo</i> studies revealed that the system could efficiently load functional mRNAs to the EVs. Furthermore, adipose specific delivery of loaded <i>Pgc1α</i> mRNA via the strategy could efficiently induce white adipocyte browning. Similarly, delivery of interleukin-10 (<i>Il-</i>10) mRNA via the strategy had potent anti-inflammatory effect in inflammatory bowel disease (IBD) mouse model. Together, our study has proposed an efficient strategy to load therapeutic mRNAs of interest into EVs, which could be used as a promising strategy for gene therapy.