A cell-penetrating bispecific antibody suppresses hepatitis B virus replication and secretion

Hepatitis B virus (HBV) represents one of the major pathogenic factor that leads to chronic liver diseases and the development of hepatocellular carcinoma (HCC). The currently approved anti-HBV drugs cannot eradicate the virus or block the development of HCC. HBV nucleocapsid consists of the hepatit...

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Main Authors: Chongwei Xie, Bing Zhou, Da Yao, Xin Wang, Lihong Zhong, Chuanghua Qiu, Junfang Zhang
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Virus Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S0168170225000073
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author Chongwei Xie
Bing Zhou
Da Yao
Xin Wang
Lihong Zhong
Chuanghua Qiu
Junfang Zhang
author_facet Chongwei Xie
Bing Zhou
Da Yao
Xin Wang
Lihong Zhong
Chuanghua Qiu
Junfang Zhang
author_sort Chongwei Xie
collection DOAJ
description Hepatitis B virus (HBV) represents one of the major pathogenic factor that leads to chronic liver diseases and the development of hepatocellular carcinoma (HCC). The currently approved anti-HBV drugs cannot eradicate the virus or block the development of HCC. HBV nucleocapsid consists of the hepatitis B core antigen (HBcAg) and the HBV relaxed-circular partially double-stranded DNA (rcDNA), indispensable in virus replication. The present study reported a cell-penetrating bispecific antibody targeting HBcAg and preS1, fused with the cell-penetrating peptide R9TAT, named Anti-preS1 × Anti-HBcAg-R9TAT. The antibody could recognize preS1 and HBcAg and internalize into living cells efficiently, suppressing the extracellular hepatitis B surface antigen (HBsAg) and hepatitis B envelope antigen, and the intracellular HBsAg and HBcAg in vitro. This cell-penetrating bispecific antibody is a novel approach to suppressing HBV replication and secretion and is a promising anti-HBV therapeutic antibody candidate.
format Article
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institution Kabale University
issn 1872-7492
language English
publishDate 2025-03-01
publisher Elsevier
record_format Article
series Virus Research
spelling doaj-art-5166cb61916b414cac32690bfecc331f2025-02-02T05:26:39ZengElsevierVirus Research1872-74922025-03-01353199531A cell-penetrating bispecific antibody suppresses hepatitis B virus replication and secretionChongwei Xie0Bing Zhou1Da Yao2Xin Wang3Lihong Zhong4Chuanghua Qiu5Junfang Zhang6Medical Research Center, Yuebei People's Hospital, Shantou University Medical College, 512025, Shaoguan, China; Shenzhen Immuthy Biotech Co., Ltd, 518107, Shenzhen, Guangdong, ChinaInstitute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, 518112, Shenzhen, Guangdong, ChinaThe First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 518037, Shenzhen, Guangdong, ChinaInstitute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, 518112, Shenzhen, Guangdong, ChinaThe First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 518037, Shenzhen, Guangdong, ChinaThe First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 518037, Shenzhen, Guangdong, China; Corresponding author at: The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002 Sungang Road, Shenzhen, Guangdong, China.Medical Research Center, Yuebei People's Hospital, Shantou University Medical College, 512025, Shaoguan, China; Shenzhen Immuthy Biotech Co., Ltd, 518107, Shenzhen, Guangdong, China; Corresponding author at: Shenzhen Immuthy Biotech Co., Ltd, Shenzhen, China, Medical Research Center, Yuebei People's Hospital, Shantou University Medical College, 512025, 133 Huimin Road, Shaoguan, China.Hepatitis B virus (HBV) represents one of the major pathogenic factor that leads to chronic liver diseases and the development of hepatocellular carcinoma (HCC). The currently approved anti-HBV drugs cannot eradicate the virus or block the development of HCC. HBV nucleocapsid consists of the hepatitis B core antigen (HBcAg) and the HBV relaxed-circular partially double-stranded DNA (rcDNA), indispensable in virus replication. The present study reported a cell-penetrating bispecific antibody targeting HBcAg and preS1, fused with the cell-penetrating peptide R9TAT, named Anti-preS1 × Anti-HBcAg-R9TAT. The antibody could recognize preS1 and HBcAg and internalize into living cells efficiently, suppressing the extracellular hepatitis B surface antigen (HBsAg) and hepatitis B envelope antigen, and the intracellular HBsAg and HBcAg in vitro. This cell-penetrating bispecific antibody is a novel approach to suppressing HBV replication and secretion and is a promising anti-HBV therapeutic antibody candidate.http://www.sciencedirect.com/science/article/pii/S0168170225000073Cell-penetrating bispecific antibodyHBcAgCell-penetrating peptideHBV
spellingShingle Chongwei Xie
Bing Zhou
Da Yao
Xin Wang
Lihong Zhong
Chuanghua Qiu
Junfang Zhang
A cell-penetrating bispecific antibody suppresses hepatitis B virus replication and secretion
Virus Research
Cell-penetrating bispecific antibody
HBcAg
Cell-penetrating peptide
HBV
title A cell-penetrating bispecific antibody suppresses hepatitis B virus replication and secretion
title_full A cell-penetrating bispecific antibody suppresses hepatitis B virus replication and secretion
title_fullStr A cell-penetrating bispecific antibody suppresses hepatitis B virus replication and secretion
title_full_unstemmed A cell-penetrating bispecific antibody suppresses hepatitis B virus replication and secretion
title_short A cell-penetrating bispecific antibody suppresses hepatitis B virus replication and secretion
title_sort cell penetrating bispecific antibody suppresses hepatitis b virus replication and secretion
topic Cell-penetrating bispecific antibody
HBcAg
Cell-penetrating peptide
HBV
url http://www.sciencedirect.com/science/article/pii/S0168170225000073
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