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, Chulhee Choi

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122 Citations (Scopus)

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.

Original languageEnglish
Article number12277
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 2016 Jul 22

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

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    Yim, N., Ryu, S. W., Choi, K., Lee, K. R., Lee, S., Choi, H., Kim, J., Shaker, M. R., Sun, W., Park, J. H., Kim, D., Do Heo, W., & Choi, C. (2016). Exosome engineering for efficient intracellular delivery of soluble proteins using optically reversible protein-protein interaction module. Nature Communications, 7, [12277]. https://doi.org/10.1038/ncomms12277