Antiviral effect of hepatitis B virus S gene-specific anti-gene locked nucleic acid in transgenic mice
10.3760/cma.j.issn.1007-3418.2018.01.006
- VernacularTitle: 针对乙型肝炎病毒S编码链的反基因锁核酸在转基因小鼠体内的抗病毒效果
- Author:
Shurong XIAO
1
;
Guidan XU
;
Wujun WEI
;
Bin PENG
;
Yibin DENG
Author Information
1. Centre for Medical Laboratory Science, the Affiliated Hospital of Youjiang Medical College for Nationalities, Baise 533000, China
- Publication Type:Journal Article
- Keywords:
Hepatitis B virus;
Hepatitis B;
Anti-gene therapy;
Locked nucleic acid
- From:
Chinese Journal of Hepatology
2018;26(1):17-22
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the antiviral effect of hepatitis B virus (HBV) S gene-specific anti-gene locked nucleic acid (LNA) in transgenic mice.
Methods:A total of 30 HBV transgenic mice were randomly divided into blank control group (5% glucose + liposome), unrelated sequence control group, lamivudine control group, antisense LNA control group, and anti-gene LNA group, with 6 mice in each group. The mice in the lamivudine group were given lamivudine by gavage, and LNA was injected via the caudal vein. Quantitative real-time PCR was used to measure serum HBV DNA, ELISA was used to measure serum HBsAg, RT-PCR was used to measure HBV S mRNA level in the liver, and immunohistochemistry was used to measure the level of HBsAg in hepatocytes.
Results:At 3, 5, and 7 days after treatment, there were significant changes in the inhibition rates of HBV DNA (37.18%, 50.27%, and 61.46%, respectively) and HBsAg (30.17%, 44.00%, and 57.76%, respectively) achieved by anti-gene LNA (P < 0.01), and there were significant differences between the anti-gene LNA group and the other four control groups (P < 0.05). In the anti-gene LNA group, the relative mRNA expression of HBV S gene was 0.33 and the percentage of HBsAg-positive hepatocytes was 31%, which were significantly different from these two indices in the control groups (P < 0.05). There were no abnormal changes in liver/renal biochemical parameters and HE staining results.
Conclusion:Anti-gene LNA targeting at HBV S gene has a strong antiviral effect in transgenic mice, which provides theoretical and experimental bases for gene therapy for HBV.