title: Engineering of bacterial exotoxins for highly efficient and receptor-specific intracellular delivery of diverse cargos.
abstract: The intracellular delivery of proteins with high efficiency in a receptor-specific manner is of great significance in molecular medicine and biotechnology, but remains a challenge. Herein, we present the development of a highly efficient and receptor-specific delivery platform for protein cargos by combining the receptor binding domain of Escherichia coli Shiga-like toxin and the translocation domain of Pseudomonas aeruginosa exotoxin A. We demonstrated the utility and efficiency of the delivery platform by showing a cytosolic delivery of diverse proteins both in vitro and in vivo in a receptor-specific manner. In particular, the delivery system was shown to be effective for targeting an intracellular protein and consequently suppressing the tumor growth in xenograft mice. The present platform can be widely used for intracellular delivery of diverse functional macromolecules with high efficiency in a receptor-specific manner. Biotechnol. Bioeng. 2016;113: 1639-1646. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea.
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Ryou
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea.
authors.forename: Yoo-Kyoung
authors.initials: YK
authors.lastname: Sohn
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea.
authors.forename: Da-Eun
authors.initials: DE
authors.lastname: Hwang
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea.
authors.forename: Woo-Yong
authors.initials: WY
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea.
authors.forename: Nury
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea.
authors.forename: Won-Do
authors.initials: WD
authors.lastname: Heo
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea. hskim76@kaist.ac.kr.
authors.forename: Hak-Sung
authors.initials: HS
authors.lastname: Kim
mesh_terms: D036002:ADP Ribose Transferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005098:Exotoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D042541:Intracellular Space / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015202:Protein Engineering / Q000379:methods*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D022603:Shiga Toxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D005098:Exotoxins; D011993:Recombinant Fusion Proteins; D022603:Shiga Toxins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
keywords: bacterial toxin; cytosolic delivery; intracellular delivery; protein delivery; protein engineering