title: Exosome engineering for efficient intracellular delivery of soluble proteins using optically reversible protein-protein interaction module.
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.
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Korea.
authors.forename: Nambin
authors.initials: N
authors.lastname: Yim
authors.affiliation: Cellex Life Sciences Inc., Daejeon, 34141, Korea.
authors.forename: Seung-Wook
authors.initials: SW
authors.lastname: Ryu
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Korea. ccbioks@kaist.ac.kr.
authors.forename: Kyungsun
authors.initials: K
authors.lastname: Choi
authors.affiliation: Cellex Life Sciences Inc., Daejeon, 34141, Korea.
authors.forename: Kwang Ryeol
authors.initials: KR
authors.lastname: Lee
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Korea.
authors.forename: Seunghee
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Korea.
authors.forename: Hojun
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon, 34141, Korea.
authors.forename: Jeongjin
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Brain Korea 21 Program, Korea University College of Medicine, Seoul, 02841, Korea.
authors.forename: Mohammed R
authors.initials: MR
authors.lastname: Shaker
authors.affiliation: Department of Anatomy, Brain Korea 21 Program, Korea University College of Medicine, Seoul, 02841, Korea.
authors.forename: Woong
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Korea.
authors.forename: Ji-Ho
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon, 34141, Korea.
authors.forename: Daesoo
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon, 34141, Korea.|Cancer Metastasis Control Center, KAIST Institute for the Biocentury, KAIST, Daejeon, 34141, Korea.|Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon, 34047, Korea.
authors.forename: Won Do
authors.initials: WD
authors.lastname: Heo
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Korea. cchoi@kaist.ac.kr.|Cellex Life Sciences Inc., Daejeon, 34141, Korea. cchoi@kaist.ac.kr.|Cancer Metastasis Control Center, KAIST Institute for the Biocentury, KAIST, Daejeon, 34141, Korea. cchoi@kaist.ac.kr.
authors.forename: Chulhee
authors.initials: C
authors.lastname: Choi
mesh_terms: D000818:Animals; D029681:Arabidopsis Proteins; D051792:Basic Helix-Loop-Helix Proteins; D056931:Cryptochromes; D016503:Drug Delivery Systems; D055354:Exosomes; D005818:Genetic Engineering; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008822:Mice, Transgenic; D061848:Optical Imaging; D011994:Recombinant Proteins / Q000008:administration & dosage*
chemical_list: D029681:Arabidopsis Proteins; D051792:Basic Helix-Loop-Helix Proteins; D056931:Cryptochromes; D011994:Recombinant Proteins; C533832:CIB1 protein, Arabidopsis; C103618:CRY2 protein, Arabidopsis