表达干扰素-lambda-3的小环DNA载体可抑制乙型肝炎病毒的复制

StephenW

BMC Mol Cell Biol. 2020 Feb 18;21(1):6. doi: 10.1186/s12860-020-00250-9.
Minicircle DNA vector expressing interferon-lambda-3 inhibits hepatitis B virus replication and expression in hepatocyte-derived cell line.
Guo X1, Chen D2, Cai Q3, Huang Z1, Xu W1, Peng L4, Chen P5.
Author information

1
    Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
2
    Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
3
    Department of Hepatology, The Third People's Hospital of Shenzhen, Shenzhen, China.
4
    Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. [email protected].
5
    Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. [email protected].

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:

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

PMID:
    32070272
DOI:
    10.1186/s12860-020-00250-9

StephenW

BMC分子细胞生物学。 2020年2月18日; 21（1）：6。 doi：10.1186 / s12860-020-00250-9。
表达干扰素-lambda-3的小环DNA载体可抑制乙型肝炎病毒的复制和在肝细胞衍生细胞系中的表达。
郭X1，陈D2，蔡Q3，黄Z1，徐W1，彭L4，陈P5。
作者信息

1个
    中山大学附属第三医院传染病科，广州
2
    中山大学附属第六医院肿瘤内科，广州
3
    深圳市第三人民医院肝科
4
    中山大学附属第三医院传染病科，广州[email protected]。
5
    中国科学院深圳先进技术研究所，中国深圳。 [email protected]。

抽象
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，但严重的全身性副作用限制了其临床应用。具有可比的抗病毒活性且毒性较小的干扰素-λ（IFNλ）被认为是IFNα的良好替代干扰素。另外，基因载体介导的治疗产物在靶细胞/组织中的可持续表达可以克服由IFNs半衰期短引起的缺点。
结果：

我们在肝细胞特异性ApoE启动子（MC.IFNλ3）的控制下构建了表达肝特异性IFNλ3的微圆（MC）载体，并在表达HBV的肝细胞衍生的细胞模型（HepG2.2.15）中研究了其抗HBV活性。 ）。如预期的那样，就能够通过激活HepG2中干扰素刺激基因（ISG）的表达抑制病毒抗原表达和病毒DNA复制而言，能够在受体肝细胞中表达IFNλ3的MC.IFNλ3载体表现出强大的抗HBV活性。 2.15格。
结论：

鉴于MC载体可轻松递送到肝脏中，因此，针对肝脏的IFN基因转移（MC.IFNλ3）代替了反复全身性施用IFN，为治疗慢性HBV感染提供了一个有希望的概念。
关键字：

乙型肝炎病毒；干扰素刺激基因；微圆DNA; III型干扰素

PMID：
    32070272
DOI：
    10.1186 / s12860-020-00250-9

StephenW

https://bmcmolcellbiol.biomedcen ... /s12860-020-00250-9