DNA-programmed Stem Cell Niches via Orthogonal Extracellular Vesicle-Cell Communications.

Abstract

Extracellular vesicles (EVs) are natural carriers for intercellular transfer of bioactive molecules, which have been harnessed for wide biomedical applications. However, a facile yet general approach to engineering interspecies EV-cell communications is still lacking. Here, w e report the use of DNA to encode the heterogeneous interfaces of EVs and cells in a manner free of covalent or genetic modifications, which enables orthogonal EV-cell interkingdom interactions in complex environments. W e employ cholesterol-modified DNA strands and tetrahedral DNA frameworks with complementary sequences to serve as artificial ligands and receptors docking on EVs and living cells, respectively, which can mediate specific yet efficient cellular internalization of EVs via Watson-Crick base pairing. W e show that based on this system, human cells can adopt EVs derived from the mouse, watermelon, and E. coli. By implementing several EV-cell circuits, w e show that this DNA-programmed system allows orthogonal EV-cell communications in complex environments. W e further demonstrate efficient delivery of EVs with bioactive contents derived from STO cells toward monkey female germline stem cells (FGSCs), which enables self-renewal and stemness maintenance of the FGSCs without feeder cells. This system might provide a universal platform to customize intercellular exchanges of materials and signals across species and kingdoms. This article is protected by copyright. All rights reserved.