title: Malaria sporozoite protein expression enhances baculovirus-mediated gene transfer to hepatocytes.
abstract: BACKGROUND
  Baculovirus vector (BV) is able to transduce foreign genes into mammalian cells efficiently and safely by incorporating a mammalian promoter. In the present study, we tailored the surface proteins expressed by malaria sporozoites to enhance hepatocyte transduction. Sporozoites infect hepatocytes within minutes of initial entry into the blood circulation. Infectivity and hepatocyte-specific selectivity are mediated by the interplay between hepatocytes and sporozoite surface proteins. The circumsporozoite protein (CSP) and the thrombospondin-related anonymous protein (TRAP) bind to the heparan sulfate proteoglycan on the hepatocyte surface and contribute to sporozoite infection and hepatocyte selectivity.
  
  
  METHODS
  BVs displaying an ectodomain consisting of three different CSP variants (full-length, N-terminal and C-terminal) or TRAP on the virus envelope were constructed, and the resulting in vitro hepatocyte transduction efficiency was evaluated.
  
  
  RESULTS
  We demonstrated improved hepatocyte transduction efficiency in BVs expressing CSP or TRAP ectodomains compared to BVs without malaria surface proteins. In addition, gene transduction efficiencies for BVs displaying CSP or TRAP are higher than those expressing the preS1 antigen of the hepatitis B virus.
  
  
  CONCLUSIONS
  BVs expressing CSP or TRAP in the ectodomain could represent a promising hepatocyte-specific gene delivery methodology. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Laboratory of Vaccinology and Applied Immunology, Kanazawa University, School of Pharmacy, Kanazawa, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Tamura
authors.affiliation: Laboratory of Vaccinology and Applied Immunology, Kanazawa University, School of Pharmacy, Kanazawa, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kawabata
authors.affiliation: Laboratory of Vaccinology and Applied Immunology, Kanazawa University, School of Pharmacy, Kanazawa, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Matsushita
authors.affiliation: Electron Microscope Room, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
authors.forename: Miako
authors.initials: M
authors.lastname: Sakaguchi
authors.affiliation: Laboratory of Vaccinology and Applied Immunology, Kanazawa University, School of Pharmacy, Kanazawa, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D056945:Hep G2 Cells; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism* / Q000469:parasitology; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D010963:Plasmodium falciparum / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D061987:Sf9 Cells; D018411:Spodoptera
chemical_list: D019812:Heparan Sulfate Proteoglycans; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; C069428:thrombospondin-related adhesive protein, protozoan
keywords: baculovirus vectors; circumsporozoite protein; gene transduction; hepatocytes; thrombospondin-related anonymous protein