乙型肝炎病毒（HBV）感染是一个全球公共卫生问题。目前用于慢性乙肝患者治疗的药物主要有干扰素α和核苷类似物，但因较大的免疫副作用和病毒耐药性而受限，现急需开发新型的治疗方法。基因治疗是一种安全、有效的疾病治疗方法，目前已运用于多种癌症治疗，如黑色素瘤等。我们前期研究发现，宿主基因FAM176A在体外和动物体内能有效抑制HBV的复制和基因表达，但具体作用机制还未阐明；该基因仅编码152个氨基酸，具有潜在治疗慢性乙型肝炎的潜能。本研究将阐明FAM176A抗乙肝病毒的作用机制，优化并筛选出无（低）毒性、高效抑制HBV的FAM176A功能片段；采用基于腺相关病毒（AAV）基因治疗载体，研究FAM176A或其功能片段治疗慢性乙肝人肝嵌合鼠模型的效果和安全性。

Hepatitis B Virus (HBV) infection is a global concern of public health. Current therapeutics for chronic hepatitis B, including interferon-alpha and nucleos(t)ide analogues, are limited by immune side effects and drug resistance. New therapeutics with higher efficacy and safety remain an unmet need. Gene therapy is regarded as a safe and effective therapeutic for multiple human cancers like melanoma. Our previous study showed that host gene FAM176A efficiently inhibits HBV replication and gene expression both in vitro and in vivo, but its detailed mechanism is barely understood. This gene encodes 152 amino acids and has shown therapeutic potential against chronic hepatitis B. This study aims to clarify the antiviral mechanism of FAM176A, identify and optimize FAM176A functional fragments efficiently against HBV with no or low toxicity, and use gene therapy vectors like adeno-related virus (AAV) to further evaluate the antiviral effect and safety of FAM176A and/or its functional fragments in human liver chimeric mice with chronic HBV infection.