一种细胞穿透性双特异性抗体可抑制乙型肝炎病毒的复制和分泌。
A cell-penetrating bispecific antibody suppresses hepatitis B virus replication and secretion.
作者信息
Xie Chongwei, Zhou Bing, Yao Da, Wang Xin, Zhong Lihong, Qiu Chuanghua, Zhang Junfang
机构信息
Medical Research Center, Yuebei People's Hospital, Shantou University Medical College, 512025, Shaoguan, China; Shenzhen Immuthy Biotech Co., Ltd, 518107, Shenzhen, Guangdong, China.
Institute 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, China.
出版信息
Virus Res. 2025 Mar;353:199531. doi: 10.1016/j.virusres.2025.199531. Epub 2025 Jan 31.
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.
乙型肝炎病毒（HBV）是导致慢性肝病和肝细胞癌（HCC）发生的主要致病因素之一。目前获批的抗HBV药物无法根除病毒或阻断HCC的发展。HBV核衣壳由乙型肝炎核心抗原（HBcAg）和HBV松弛环状部分双链DNA（rcDNA）组成，这两者在病毒复制中不可或缺。本研究报道了一种靶向HBcAg和前S1的细胞穿透双特异性抗体，与细胞穿透肽R9TAT融合，命名为抗前S1×抗HBcAg-R9TAT。该抗体能够识别前S1和HBcAg，并有效地内化到活细胞中，在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，以及细胞内的HBsAg和HBcAg。这种细胞穿透双特异性抗体是抑制HBV复制和分泌的一种新方法，是一种有前景的抗HBV治疗性抗体候选药物。
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