BACKGROUND Interferon-alpha (IFNα) is a first-line treatment option for chronic hepatitis B virus (HBV) infection, but the severe systemic side-effects limited its clinical application. Interferon-lambda (IFNλ) with comparable antiviral activity and less toxic side-effects is thought to be a good alternative interferon to IFNα. Additionally, the gene vector mediated sustainably expression of therapeutic product in the target cells/tissue may overcome the shortcomings resulted from the short half-life of IFNs. RESULTS We constructed a liver-specific IFNλ3-expressing minicircle (MC) vector under the control of a hepatocyte-specific ApoE promoter (MC.IFNλ3) and investigated its anti-HBV activity in a HBV-expressing hepatocyte-derived cell model (HepG2.2.15). As expected, the MC.IFNλ3 vector capable of expressing IFNλ3 in the recipient hepatocytes has demonstrated robust anti-HBV activity, in terms of suppressing viral antigen expression and viral DNA replication, via activation the interferon-stimulated gene (ISG) expression in HepG2.2.15 cells. CONCLUSIONS Given the MC vector can be easily delivered into liver, the liver-targeted IFN gene-transfer (MC.IFNλ3), instead of systemic administrating IFN repeatedly, provides a promising concept for the treatment of chronic HBV infection.

中文翻译：

---

表达干扰素 lambda-3 的小环 DNA 载体可抑制乙型肝炎病毒在肝细胞来源的细胞系中的复制和表达。


背景干扰素-α（IFNα）是慢性乙型肝炎病毒（HBV）感染的一线治疗选择，但严重的全身副作用限制了其临床应用。干扰素-λ (IFNλ) 具有相当的抗病毒活性和较少的毒副作用，被认为是 IFNα 的良好干扰素替代品。此外，基因载体介导的治疗产物在靶细胞/组织中持续表达可以克服IFN半衰期短造成的缺点。结果我们构建了肝细胞特异性 ApoE 启动子 (MC.IFNλ3) 控制下的肝脏特异性 IFNλ3 表达小环 (MC) 载体，并在表达 HBV 的肝细胞来源细胞模型 (HepG2.3) 中研究了其抗 HBV 活性。 2.15）。正如预期的那样，能够在受体肝细胞中表达 IFNλ3 的 MC.IFNλ3 载体通过激活 HepG2 中的干扰素刺激基因 (ISG) 表达，在抑制病毒抗原表达和病毒 DNA 复制方面表现出强大的抗 HBV 活性。 2.15个细胞。结论 由于MC载体可以很容易地递送至肝脏，因此肝脏靶向IFN基因转移（MC.IFNλ3）代替重复全身施用IFN，为治疗慢性乙型肝炎病毒感染提供了一个有前景的概念。