PreS/2-21-Guided siRNA Nanoparticles Target to Inhibit Hepatitis B Virus Infection and Replication
Brief intro:
- Author: Lixia Gao, Jie Yang, Jutao Feng, Ziying Liu, Ying Dong, Jiangyan Luo, Liangzhentian Yu, Jiamei Wang, Hongying Fan, Weifeng Ma, and Tiancai Liu
- Journal: Front Immunol
- Doi: https://www.doi.org/10.3389/fimmu.2022.856463
- Publication Date: 2022 Apr 29
Products/Services used in the paper
Quotation shows PackGene:The recombinant adeno-associated virus AAV-HBV-002 applied to construct the hepatitis B model was purchased from PackGene Biotech, Co., Ltd.
Research Field:liver
AAV Serotype:AAV-HBV-002
Targeted organ:liver
Animal or cell line strain:C57BL/6J male mice
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.
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