title: Sendai viroplexes for epidermal growth factor receptor-directed delivery of interleukin-12 and salmosin genes to cancer cells.
abstract: BACKGROUND
  The effective delivery of therapeutic genes to target cells has been a fundamental goal in cancer gene therapy because of its advantages with respect to both safety and transfection efficiency. In the present, study we describe a tumor-directed gene delivery system that demonstrates remarkable efficacy in gene delivery and minimizes the off-target effects of gene transfection.
  
  
  METHODS
  The system consists of a well-verified cationic O,O'-dimyristyl-N-lysyl glutamate (DMKE), Sendai virus fusion (F) protein and hemagglutinin-neuraminidase (HN) protein, referred to as cationic Sendai F/HN virosomes. To achieve tumor-specific recognition, anti-epidermal growth factor (EGF) receptor antibody was coupled to the surface of the virosomes containing interleukin-12 (IL-12) and/or salmosin genes that have potent anti-angiogenetic functions.
  
  
  RESULTS
  Among the virosomal formulations, the anti-EGF receptor (EGFR) viroplexes, prepared via complexation of plasmid DNA (pDNA) with cationic DMKE lipid, exhibited more efficient gene transfection to tumor cells over-expressing EGF receptors compared to the neutrally-charged anti-EGFR virosomes encapsulating pDNA. In addition, the anti-EGFR viroplexes with IL-12 and salmosin genes exhibited the most effective therapeutic efficacy in a mouse tumor model. Especially when combined with doxorubicin, transfection of the two genes via the anti-EGFR viroplexes exhibited an enhanced inhibitory effect on tumor growth and metastasis in lungs.
  
  
  CONCLUSIONS
  The results of the present study suggest that anti-EGFR viroplexes can be utilized as an effective strategy for tumor-directed gene delivery. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors.forename: Jung Seok
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors.forename: Min Woo
authors.initials: MW
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors.forename: Hwa Yeon
authors.initials: HY
authors.lastname: Jeong
authors.affiliation: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors.forename: Seong Jae
authors.initials: SJ
authors.lastname: Kang
authors.affiliation: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors.forename: Sang Il
authors.initials: SI
authors.lastname: Park
authors.affiliation: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors.forename: Yeon Kyung
authors.initials: YK
authors.lastname: Lee
authors.affiliation: Department of Biomedical Laboratory Science, Korea Nazarene University, Cheonan, Republic of Korea.
authors.forename: Hong Sung
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Science, Konyang University, Daejeon, Republic of Korea.
authors.forename: Keun Sik
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors.forename: Yong Serk
authors.initials: YS
authors.lastname: Park
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D045744:Cell Line, Tumor; D003435:Crotalid Venoms / Q000235:genetics* / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods; D015707:HN Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics* / Q000378:metabolism; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D029082:Sendai virus / Q000235:genetics* / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism; D022701:Virosomes / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000903:Antibiotics, Antineoplastic; D003435:Crotalid Venoms; D015707:HN Protein; D014760:Viral Fusion Proteins; D022701:Virosomes; C115393:salmosin; D018664:Interleukin-12; D004317:Doxorubicin; D066246:ErbB Receptors
keywords: EGF receptor; Sendai virus; gene therapy; nonviral vector; pDNA delivery; tumor targeting