Exosome engineering for efficient intracellular delivery of soluble proteins using optically reversible protein–protein interaction module

Nambin Yim, Seung-Wook Ryu, Kyungsun Choi (), Kwang Ryeol Lee, Seunghee Lee, Hojun Choi, Jeongjin Kim, Mohammed R. Shaker, Woong Sun, Ji-Ho Park, Daesoo Kim, Won Do Heo and Chulhee Choi ()
Additional contact information
Nambin Yim: KAIST
Seung-Wook Ryu: Cellex Life Sciences Inc.
Kyungsun Choi: KAIST
Kwang Ryeol Lee: Cellex Life Sciences Inc.
Seunghee Lee: KAIST
Hojun Choi: KAIST
Jeongjin Kim: KAIST
Mohammed R. Shaker: Brain Korea 21 Program, Korea University College of Medicine
Woong Sun: Brain Korea 21 Program, Korea University College of Medicine
Ji-Ho Park: KAIST
Daesoo Kim: KAIST
Won Do Heo: KAIST
Chulhee Choi: KAIST

Nature Communications, 2016, vol. 7, issue 1, 1-9

Abstract: Abstract Nanoparticle-mediated delivery of functional macromolecules is a promising method for treating a variety of human diseases. Among nanoparticles, cell-derived exosomes have recently been highlighted as a new therapeutic strategy for the in vivo delivery of nucleotides and chemical drugs. Here we describe a new tool for intracellular delivery of target proteins, named ‘exosomes for protein loading via optically reversible protein–protein interactions’ (EXPLORs). By integrating a reversible protein–protein interaction module controlled by blue light with the endogenous process of exosome biogenesis, we are able to successfully load cargo proteins into newly generated exosomes. Treatment with protein-loaded EXPLORs is shown to significantly increase intracellular levels of cargo proteins and their function in recipient cells in vitro and in vivo. These results clearly indicate the potential of EXPLORs as a mechanism for the efficient intracellular transfer of protein-based therapeutics into recipient cells and tissues.

Date: 2016
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DOI: 10.1038/ncomms12277

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