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Mutation of arginine residues to avoid non-specific cellular uptakes for hepatitis B virus core particles

Mohamed Suffian, Izzat Fahimuddin and Nishimura, Yuya and Morita, Kenta and Nakamura-Tsuruta, Sachiko and Al-Jamal, Khuloud and Ishii, Jun and Ogino, Chiaki and Kondo, Akihiko (2015) Mutation of arginine residues to avoid non-specific cellular uptakes for hepatitis B virus core particles. Nanobiotechnology, 13. ISSN 1477-3155

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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.

Item Type: Article (Journal)
Additional Information: 7836/57364
Uncontrolled Keywords: Arginine, cell membranes, cells, cytology, mobile security, nucleic acids, viruses
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QR Microbiology > QR355 Virology
R Medicine > RM Therapeutics. Pharmacology
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button): Kulliyyah of Pharmacy > Department of Pharmaceutical Chemistry
Depositing User: Dr Izzat Fahimuddin Mohamed Suffian
Date Deposited: 23 Jun 2017 08:04
Last Modified: 23 Jun 2017 08:04
URI: http://irep.iium.edu.my/id/eprint/57364

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