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

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 du...

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Main Authors: Mohamed Suffian, Izzat Fahimuddin, Nishimura, Yuya, Morita, Kenta, Nakamura-Tsuruta, Sachiko, Al-Jamal, Khuloud, Ishii, Jun, Ogino, Chiaki, Kondo, Akihiko
Format: Article
Language:English
Published: Biomed Central 2015
Subjects:
Online Access:http://irep.iium.edu.my/57364/
http://irep.iium.edu.my/57364/1/Suffian%20et%20al.%20Journal%20of%20Nanobiotechnology.pdf
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author Mohamed Suffian, Izzat Fahimuddin
Nishimura, Yuya
Morita, Kenta
Nakamura-Tsuruta, Sachiko
Al-Jamal, Khuloud
Ishii, Jun
Ogino, Chiaki
Kondo, Akihiko
author_facet Mohamed Suffian, Izzat Fahimuddin
Nishimura, Yuya
Morita, Kenta
Nakamura-Tsuruta, Sachiko
Al-Jamal, Khuloud
Ishii, Jun
Ogino, Chiaki
Kondo, Akihiko
author_sort Mohamed Suffian, Izzat Fahimuddin
building IIUM Repository
collection Online Access
description 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.
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spelling iium-573642017-06-23T00:04:31Z http://irep.iium.edu.my/57364/ Mutation of arginine residues to avoid non-specific cellular uptakes for hepatitis B virus core particles Mohamed Suffian, Izzat Fahimuddin Nishimura, Yuya Morita, Kenta Nakamura-Tsuruta, Sachiko Al-Jamal, Khuloud Ishii, Jun Ogino, Chiaki Kondo, Akihiko QH301 Biology QR355 Virology RM Therapeutics. Pharmacology 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. Biomed Central 2015-02-13 Article PeerReviewed application/pdf en http://irep.iium.edu.my/57364/1/Suffian%20et%20al.%20Journal%20of%20Nanobiotechnology.pdf 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 http://dx.doi.org/10.1186/s12951-015-0074-8
spellingShingle QH301 Biology
QR355 Virology
RM Therapeutics. Pharmacology
Mohamed Suffian, Izzat Fahimuddin
Nishimura, Yuya
Morita, Kenta
Nakamura-Tsuruta, Sachiko
Al-Jamal, Khuloud
Ishii, Jun
Ogino, Chiaki
Kondo, Akihiko
Mutation of arginine residues to avoid non-specific cellular uptakes for hepatitis B virus core particles
title Mutation of arginine residues to avoid non-specific cellular uptakes for hepatitis B virus core particles
title_full Mutation of arginine residues to avoid non-specific cellular uptakes for hepatitis B virus core particles
title_fullStr Mutation of arginine residues to avoid non-specific cellular uptakes for hepatitis B virus core particles
title_full_unstemmed Mutation of arginine residues to avoid non-specific cellular uptakes for hepatitis B virus core particles
title_short Mutation of arginine residues to avoid non-specific cellular uptakes for hepatitis B virus core particles
title_sort mutation of arginine residues to avoid non-specific cellular uptakes for hepatitis b virus core particles
topic QH301 Biology
QR355 Virology
RM Therapeutics. Pharmacology
url http://irep.iium.edu.my/57364/
http://irep.iium.edu.my/57364/
http://irep.iium.edu.my/57364/1/Suffian%20et%20al.%20Journal%20of%20Nanobiotechnology.pdf