Photoactivatable Synthetic Exosomes for RNA‐Based Communication Between Artificial Cells and Living Cells

Abstract Artificial cells are self‐assembled microstructures engineered to replicate the functions of natural cells, such as the capacity to interact and communicate. Until now, communication between artificial and living cells has mainly been based on the exchange of small molecules. An important communication pathway in living systems, however, involves the exchange of bioactive molecules such as neurotransmitters and nucleic acids via their protected transport with vesicles or exosomes. Here, we describe a modular strategy to construct artificial cells able to regulate mammalian cell protein expression via vesicle‐based RNA communication. These artificial cells are assembled from amylose‐based complex coacervates stabilized by a terpolymer membrane, with polymersomes containing RNA sequestered inside. The block copolymer vesicles have photocleavable surface groups, allowing charge switching behavior and expulsion from the overall positively charged coacervate lumen. The ability of our system to transmit RNA signals to natural cells was demonstrated with in vitro artificial cell‐natural cell cocultures. Considering the crucial role of extracellular vesicles in genetic information transfer in nature, this artificial exosome design is an important step toward replicating nucleic acid communication pathways, further improving life‐like behavior in artificial cell systems.