Minicircle DNA Vector Expressing Interferon-lambda-3 Inhibits Hepatitis B Virus Replication and Expression in Hepatocyte-derived Cell Line

Overview

Journal BMC Mol Cell Biol

Publisher Biomed Central

Specialty Cell Biology

Date 2020 Feb 20

PMID 32070272

Citations 4

Authors

Xiaoyan Guo

Dianke Chen

Qingxian Cai

Zhanlian Huang

Wenxiong Xu

Liang Peng

Ping Chen

Affiliations

Soon will be listed here.

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.

Citing Articles

Review of Lambda Interferons in Hepatitis B Virus Infection: Outcomes and Therapeutic Strategies.

Novotny L, Evans J, Su L, Guo H, Meissner E Viruses. 2021; 13(6).

PMID: 34207487 PMC: 8230240. DOI: 10.3390/v13061090.

Improving therapeutic potential of non-viral minimized DNA vectors.

Arevalo-Soliz L, Hardee C, Fogg J, Corman N, Noorbakhsh C, Zechiedrich L Cell Gene Ther Insights. 2021; 6(10):1489-1505.

PMID: 33953961 PMC: 8095377. DOI: 10.18609/cgti.2020.163.

Intracellular interferon signalling pathways as potential regulators of covalently closed circular DNA in the treatment of chronic hepatitis B.

Goh Z, Ren E, Ko H World J Gastroenterol. 2021; 27(14):1369-1391.

PMID: 33911462 PMC: 8047536. DOI: 10.3748/wjg.v27.i14.1369.

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

Guo X, Chen D, Cai Q, Huang Z, Xu W, Peng L BMC Mol Cell Biol. 2020; 21(1):10.

PMID: 32122299 PMC: 7050136. DOI: 10.1186/s12860-020-00255-4.

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