Iannacone Matteo, Beccaria Cristian G, Allweiss Lena, Lucifora Julie, Tavis John E, Gehring Adam J, Dandri Maura
Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Vita-Salute San Raffaele University, 20132 Milan, Italy.
Sci Transl Med. 2025 Jul 2;17(805):eadv3678. doi: 10.1126/scitranslmed.adv3678.
Chronic hepatitis B virus (HBV) infection affects millions worldwide despite the availability of effective vaccines. The stability of HBV's genomic minichromosome (cccDNA) within hepatocytes, the persistence of integrated viral sequences capable of producing viral antigens, and the ability of the virus to evade immune control all contribute to the difficulty in achieving a functional cure. Existing antiviral treatments have minimal impact on HBV transcription, allowing persistent viral antigen production and immune dysfunction. Emerging RNA interference (RNAi) therapies targeting HBV RNAs reduce viral replication, antigen expression, and, in turn, cccDNA activity, providing a potential path to a functional cure.
尽管有有效的疫苗，但慢性乙型肝炎病毒（HBV）感染仍影响着全球数百万人。HBV基因组微型染色体（cccDNA）在肝细胞内的稳定性、能够产生病毒抗原的整合病毒序列的持久性以及病毒逃避免疫控制的能力，都导致了实现功能性治愈的困难。现有的抗病毒治疗对HBV转录的影响极小，使得病毒抗原持续产生和免疫功能障碍。新兴的针对HBV RNA的RNA干扰（RNAi）疗法可减少病毒复制、抗原表达，进而降低cccDNA活性，为功能性治愈提供了一条潜在途径。
