title: Genetically engineered and self-assembled oncolytic protein nanoparticles for targeted cancer therapy.
abstract: The integration of a targeted delivery with a tumour-selective agent has been considered an ideal platform for achieving high therapeutic efficacy and negligible side effects in cancer therapy. Here, we present engineered protein nanoparticles comprising a tumour-selective oncolytic protein and a targeting moiety as a new format for the targeted cancer therapy. Apoptin from chicken anaemia virus (CAV) was used as a tumour-selective apoptotic protein. An EGFR-specific repebody, which is composed of LRR (Leucine-rich repeat) modules, was employed to play a dual role as a tumour-targeting moiety and a fusion partner for producing apoptin nanoparticles in E. coli, respectively. The repebody was genetically fused to apoptin, and the resulting fusion protein was shown to self-assemble into supramolecular repebody-apoptin nanoparticles with high homogeneity and stability as a soluble form when expressed in E. coli. The repebody-apoptin nanoparticles showed a remarkable anti-tumour activity with negligible side effects in xenograft mice through a cooperative action of the two protein components with distinct functional roles. The repebody-apoptin nanoparticles can be developed as a systemic injectable and tumour-selective therapeutic protein for targeted cancer treatment.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea.
authors.forename: Joong-Jae
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute (KAERI), Jeongeup, Jeonbuk 580-185, South Korea.
authors.forename: Jung Ae
authors.initials: JA
authors.lastname: Kang
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea.
authors.forename: Yiseul
authors.initials: Y
authors.lastname: Ryu
authors.affiliation: Predictive Model Research Center, Korea Institute of Toxicology (KIT), Daejeon 34114, South Korea.
authors.forename: Sang-Soo
authors.initials: SS
authors.lastname: Han
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute (KAERI), Jeongeup, Jeonbuk 580-185, South Korea.
authors.forename: You Ree
authors.initials: YR
authors.lastname: Nam
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute (KAERI), Jeongeup, Jeonbuk 580-185, South Korea.
authors.forename: Jong Kook
authors.initials: JK
authors.lastname: Rho
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute (KAERI), Jeongeup, Jeonbuk 580-185, South Korea.
authors.forename: Dae Seong
authors.initials: DS
authors.lastname: Choi
authors.affiliation: Predictive Model Research Center, Korea Institute of Toxicology (KIT), Daejeon 34114, South Korea; Department of Human and Environmental Toxicology, University of Science and Technology (UST), Daejeon 34113, South Korea.
authors.forename: Sun-Woong
authors.initials: SW
authors.lastname: Kang
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute (KAERI), Jeongeup, Jeonbuk 580-185, South Korea. Electronic address: delee@kaeri.re.kr.
authors.forename: Dong-Eun
authors.initials: DE
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea. Electronic address: hskim76@kaist.ac.kr.
authors.forename: Hak-Sung
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D036022:Capsid Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D003460:Crystallization / Q000379:methods; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy / Q000379:methods*; D053758:Nanoparticles / Q000008:administration & dosage*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D050130:Oncolytic Virotherapy / Q000379:methods; D015202:Protein Engineering / Q000379:methods*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D036022:Capsid Proteins; D011994:Recombinant Proteins; C091717:VP3 protein, Chicken anemia virus
keywords: Cancer therapy; Protein nanoparticle; Repebody; Self-assembly; Targeted delivery; Tumour selectivity