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

IF 2.5 4区医学 Q3 VIROLOGY

Virus research Pub Date : 2025-01-31 DOI:10.1016/j.virusres.2025.199531

Chongwei Xie , Bing Zhou , Da Yao , Xin Wang , Lihong Zhong , Chuanghua Qiu , Junfang Zhang

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引用次数: 0

Abstract

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.

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细胞穿透双特异性抗体抑制乙型肝炎病毒的复制和分泌。

乙型肝炎病毒（HBV）是导致慢性肝病和肝细胞癌（HCC）发展的主要致病因素之一。目前批准的抗hbv药物不能根除病毒或阻止HCC的发展。HBV核衣壳由HBV核心抗原（HBcAg）和HBV松弛环部分双链DNA （rcDNA）组成，这是病毒复制中不可或缺的。本研究报道了一种靶向HBcAg和preS1的细胞穿透双特异性抗体，与细胞穿透肽R9TAT融合，命名为Anti-preS1 × Anti-HBcAg-R9TAT。该抗体能识别preS1和HBcAg并有效内化到活细胞中，体外抑制细胞外乙型肝炎表面抗原（HBsAg）和乙型肝炎包膜抗原，以及细胞内HBsAg和HBcAg。这种细胞穿透双特异性抗体是一种抑制HBV复制和分泌的新方法，是一种很有前途的抗HBV治疗抗体候选。

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来源期刊

Virus research 医学-病毒学

CiteScore

9.50

自引率

2.00%

发文量

239

审稿时长

43 days

期刊介绍： Virus Research provides a means of fast publication for original papers on fundamental research in virology. Contributions on new developments concerning virus structure, replication, pathogenesis and evolution are encouraged. These include reports describing virus morphology, the function and antigenic analysis of virus structural components, virus genome structure and expression, analysis on virus replication processes, virus evolution in connection with antiviral interventions, effects of viruses on their host cells, particularly on the immune system, and the pathogenesis of virus infections, including oncogene activation and transduction.