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Delivering mRNAs to mouse tissues using the SEND system

Ohtsuka, M.; Imafuku, J.; Hori, S.; Kurosaki, A.; Nakamura, A.; Nakahara, T.; Yahata, T.; Bhat, K.; Papastefan, S.; Nakagawa, S.; Quadros, R. M.; Miura, H.; Gurumurthy, C. B.

2023-01-29 genomics
10.1101/2023.01.28.522652 bioRxiv
Show abstract

mRNAs produced in a cell are almost always translated within the same cell. Some mRNAs are transported to other cells of the organism through processes involving membrane nanotubes or extracellular vesicles. A recent report describes a surprising new phenomenon of encapsulating mRNAs inside virus-like particles (VLPs) to deliver them to other cells in a process that was named SEND (Selective Endogenous eNcapsidation for cellular Delivery). Although the seminal work demonstrates the SEND process in cultured cells, it is unknown whether this phenomenon occurs in vivo. Here, we demonstrate the SEND process in living organisms using specially designed genetically engineered mouse models. Our proof of principle study lays a foundation for the SEND-VLP system to potentially be used as a gene therapy tool to deliver therapeutically important mRNAs to tissues.

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