title: Mutation of arginine residues to avoid non-specific cellular uptakes for hepatitis B virus core particles.
abstract: BACKGROUND
  The hepatitis B virus core (HBc) particle is known as a promising new carrier for the delivery of drugs and nucleic acids. However, since the arginine-rich domain that is located in the C-terminal region of the HBc monomer binds to the heparan sulphate proteoglycan on the cell surface due to its positive charge, HBc particles are introduced non-specifically into a wide range of cells. To avoid non-specific cellular uptake with the intent to control the ability of cell targeting, we individually replaced the respective arginine (R) residues of the arginine-rich domain located in amino acid positions 150-159 in glycine (G) residues.
  
  
  RESULTS
  The mutated HBc particles in which R154 was replaced with glycine (G) residue (R154G) showed a drastic decrease in the ability to bind to the heparan sulphate proteoglycan and to avoid non-specific cellular uptake by several types of cancer cells.
  
  
  CONCLUSIONS
  Because this mutant particle retains most of its C-terminal arginine-rich residues, it would be useful in the targeting of specificity-altered HBc particles in the delivery of nucleic acids.
authors.affiliation: Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Kobe, Japan. izzat_fahimuddin.bin_mohamed_suffian@kcl.ac.uk.|Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicine, King's College London, London, UK. izzat_fahimuddin.bin_mohamed_suffian@kcl.ac.uk.
authors.forename: Izzat Fahimuddin
authors.initials: IF
authors.lastname: Bin Mohamed Suffian
authors.affiliation: Organization of Advanced Science and Technology, Kobe University, Kobe, Japan. nyuya@landscape.kobe-u.ac.jp.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Kobe, Japan. 121t471t@stu.kobe-u.ac.jp.
authors.forename: Kenta
authors.initials: K
authors.lastname: Morita
authors.affiliation: Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Kobe, Japan. sachiko-tsuruta@rabbit.kobe-u.ac.jp.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Nakamura-Tsuruta
authors.affiliation: Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicine, King's College London, London, UK. Khuloud.al-jamal@kcl.ac.uk.
authors.forename: Khuloud T
authors.initials: KT
authors.lastname: Al-Jamal
authors.affiliation: Organization of Advanced Science and Technology, Kobe University, Kobe, Japan. junjun@port.kobe-u.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Ishii
authors.affiliation: Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Kobe, Japan. ochiaki@port.kobe-u.ac.jp.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Ogino
authors.affiliation: Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Kobe, Japan. akondo@kobe-u.ac.jp.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kondo
mesh_terms: D019943:Amino Acid Substitution; D001120:Arginine / Q000235:genetics*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D005453:Fluorescence; D005998:Glycine / Q000235:genetics; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006515:Hepatitis B virus / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D018625:Microscopy, Atomic Force; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D020349:Surface Plasmon Resonance
chemical_list: D004337:Drug Carriers; D019812:Heparan Sulfate Proteoglycans; D001120:Arginine; D005998:Glycine