Brief intro:
- Author: Yaping Wang, Liliangzi Guo, Jingrong Shi, Jingyun Li, Yanling Wen, Guoming Gu, Jianping Cui, Chengqian Feng, Mengling Jiang, Qinghong Fan, Jingyan Tang, Sisi Chen, Jun Zhang, Xiaowen Zheng, Meifang Pan, Xinnian Li, Yanxia Sun, Zheng Zhang, Xian Li, Fengyu Hu, Liguo Zhang, Xiaoping Tang & Feng Li
- Journal: Nat Commun
- Doi: https://www.doi.org/10.1038/s41467-023-43078-5
- Publication Date: 2023 Nov 15
Products/Services used in the paper
Quotation shows PackGene:rAAV8-1.3HBV, genotype C, adr (PackGene Biotech, Guangzhou, China) in 100 μl PBS buffer.
Research Field:HBV
Abstract
The underlying mechanism of chronic hepatitis B virus (HBV) functional cure by interferon (IFN), especially in patients with low HBsAg and/or young ages, is still unresolved due to the lack of surrogate models. Here, we generate a type I interferon receptor humanized mouse (huIFNAR mouse) through a CRISPR/Cas9-based knock-in strategy. Then, we demonstrate that human IFN stimulates gene expression profiles in huIFNAR peripheral blood mononuclear cells (PBMCs) are similar to those in human PBMCs, supporting the representativeness of this mouse model for functionally analyzing human IFN in vivo. Next, we reveal the tissue-specific gene expression atlas across multiple organs in response to human IFN treatment; this pattern has not been reported in healthy humans in vivo. Finally, by using the AAV-HBV model, we test the antiviral effects of human interferon. Fifteen weeks of human PEG-IFNα2 treatment significantly reduces HBsAg and HBeAg and even achieves HBsAg seroconversion. We observe that activation of intrahepatic monocytes and effector memory CD8 T cells by human interferon may be critical for HBsAg suppression. Our huIFNAR mouse can authentically respond to human interferon stimulation, providing a platform to study interferon function in vivo. PEG-IFNα2 treatment successfully suppresses intrahepatic HBV replication and achieves HBsAg seroconversion.
About PackGene
PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.
