PreS/2-21-Guided siRNA 纳米颗粒靶向抑制乙型肝炎病毒感染和复制

StephenW

PreS/2-21-Guided siRNA 纳米颗粒靶向抑制乙型肝炎病毒感染和复制
高丽霞 1 , 杨杰 1 , 冯巨涛 2 , 刘子莹 3 , 董颖 4 , 罗江艳 1 , 梁振天 1 , 王家美 1 , 范红英 1 , 马伟峰 1 , 刘天才 4
隶属关系
隶属关系

    1
    南方医科大学公共卫生学院微生物学系，广州，中国。
    2
    【作者单位】： 广州医科大学第一附属医院肝胆外科;
    3
    器官衰竭研究国家重点实验室，广东省病毒性肝炎研究重点实验室，南方医科大学南方医院传染病科，广州，中国。
    4
    南方医科大学检验医学与生物技术学院抗体工程研究所，广州，中国。

    PMID：35572586 PMCID：PMC9098953 DOI：10.3389/fimmu.2022.856463

抽象的

需要一种可行的疗法来克服无法治愈的慢性乙型肝炎（CHB）的僵局。肝细胞核中共价闭合环状DNA（cccDNA）和整合的HBV DNA的长期存在是CHB的根本原因。因此，成功抑制 HBV DNA 复制并消除 cccDNA 至关重要。最近的研究证明，RNA 干扰可以抑制靶基因的表达，从而减少 HBV 复制。然而，siRNA在体内容易被RNA酶降解，难以成功传递，缺乏组织靶向性。为了利用 siRNA 技术的优势同时克服其局限性，我们设计了一种新的策略并制备了由 PreS/2-21 肽引导并精确加载 HBV siRNA 的仿生纳米颗粒。对这些纳米粒子的体外和体内实验表明，它们体积小、稳定、安全、靶向性强，对HBV DNA、pgRNA、cccDNA、HBeAg和HBsAg具有高度抑制作用。载有 HBV 基因治疗药物的 PreS/2-21 定向纳米颗粒有望用于慢性乙型肝炎的治疗。

关键词：乙肝；脂质体纳米颗粒；肽； siRNA；瞄准。

版权所有 © 2022 高、杨、冯、刘、董、罗、于、王、范、马、刘。

StephenW

PreS/2-21-Guided siRNA Nanoparticles Target to Inhibit Hepatitis B Virus Infection and Replication
Lixia Gao  1 , Jie Yang  1 , Jutao Feng  2 , Ziying Liu  3 , Ying Dong  4 , Jiangyan Luo  1 , Liangzhentian Yu  1 , Jiamei Wang  1 , Hongying Fan  1 , Weifeng Ma  1 , Tiancai Liu  4
Affiliations
Affiliations

    1
    Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, China.
    2
    Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
    3
    State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
    4
    Institute of Antibody Engineering, School of Laboratory Medicine & Biotechnology, Southern Medical University, Guangzhou, China.

    PMID: 35572586 PMCID: PMC9098953 DOI: 10.3389/fimmu.2022.856463

Abstract

A viable therapy is needed to overcome the deadlock of the incurable chronic hepatitis B (CHB). The prolonged existence of covalently closed circular DNA (cccDNA) and integrated HBV DNA in the nucleus of hepatocytes is the root cause of CHB. As a result, it is critical to successfully suppress HBV DNA replication and eliminate cccDNA. RNA interference has been proven in recent research to silence the expression of target genes and thereby decrease HBV replication. However, siRNA is susceptible to be degraded by RNA enzymes in vivo, making it difficult to deliver successfully and lacking of tissue targeting. To exploit the advantages of siRNA technology while also overcoming its limitations, we designed a new strategy and prepared biomimetic nanoparticles that were directed by PreS/2-21 peptides and precisely loaded HBV siRNA. Experiments on these nanoparticles in vitro and in vivo revealed that they are tiny, stable, safe and highly targetable, with high inhibitory effects on HBV DNA, pgRNA, cccDNA, HBeAg and HBsAg. PreS/2-21-directed nanoparticles loaded with HBV gene therapy drugs are expected to be promising for the treatment of CHB.

Keywords: HBV; liposomal nanoparticles; peptide; siRNA; targeting.

Copyright © 2022 Gao, Yang, Feng, Liu, Dong, Luo, Yu, Wang, Fan, Ma and Liu.

StephenW

https://www.frontiersin.org/arti ... mmu.2022.856463/pdf