Minicircle DNA vector expressing interferon-lambda-3 inhibits hepatitis B virus replication and expression in hepatocyte-derived cell line

Abstract

Abstract 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.

Keywords

• Minicircle DNA
• Type III interferon
• Interferon-stimulated gene
• Hepatitis B virus