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Inhibition of HBV Expression in HBV Transgenic Mice Using AAV-Delivered CRISPR-SaCas9

The chronic production of hepatitis B viral (HBV) antigens could cause inflammation and necrosis, leading to elevation of liver enzymes from necrotic hepatocytes, hepatitis, cirrhosis, hepatocellular carcinoma, and liver failure. However, no current treatment is capable of significantly reducing HBs...

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Autores principales: Li, Hao, Sheng, Chunyu, Liu, Hongbo, Wang, Shan, Zhao, Jiangyun, Yang, Lang, Jia, Leili, Li, Peng, Wang, Ligui, Xie, Jing, Xu, Dongping, Sun, Yansong, Qiu, Shaofu, Song, Hongbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141737/
https://www.ncbi.nlm.nih.gov/pubmed/30254645
http://dx.doi.org/10.3389/fimmu.2018.02080
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author Li, Hao
Sheng, Chunyu
Liu, Hongbo
Wang, Shan
Zhao, Jiangyun
Yang, Lang
Jia, Leili
Li, Peng
Wang, Ligui
Xie, Jing
Xu, Dongping
Sun, Yansong
Qiu, Shaofu
Song, Hongbin
author_facet Li, Hao
Sheng, Chunyu
Liu, Hongbo
Wang, Shan
Zhao, Jiangyun
Yang, Lang
Jia, Leili
Li, Peng
Wang, Ligui
Xie, Jing
Xu, Dongping
Sun, Yansong
Qiu, Shaofu
Song, Hongbin
author_sort Li, Hao
collection PubMed
description The chronic production of hepatitis B viral (HBV) antigens could cause inflammation and necrosis, leading to elevation of liver enzymes from necrotic hepatocytes, hepatitis, cirrhosis, hepatocellular carcinoma, and liver failure. However, no current treatment is capable of significantly reducing HBsAg expression in patients. Our previous studies had confirmed the ability of CRISPR-Cas9 in disrupting HBV cccDNA. Here, to inhibit HBV expression efficiently in the mouse model of chronic HBV infection, the miniaturized CRISPR-SaCas9 system compatible with a HBV core region derived guide-RNA had been packaged in recombinant adeno-associated virus (AAV) type 8, which lowered the levels of serum HBsAg, HBeAg, and HBV DNA efficiently in HBV transgenic mice during 58 days continuous observation after vein injection. It further confirms the potential of the CRISPR-Cas9 technique for use in hepatitis B gene therapy.
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spelling pubmed-61417372018-09-25 Inhibition of HBV Expression in HBV Transgenic Mice Using AAV-Delivered CRISPR-SaCas9 Li, Hao Sheng, Chunyu Liu, Hongbo Wang, Shan Zhao, Jiangyun Yang, Lang Jia, Leili Li, Peng Wang, Ligui Xie, Jing Xu, Dongping Sun, Yansong Qiu, Shaofu Song, Hongbin Front Immunol Immunology The chronic production of hepatitis B viral (HBV) antigens could cause inflammation and necrosis, leading to elevation of liver enzymes from necrotic hepatocytes, hepatitis, cirrhosis, hepatocellular carcinoma, and liver failure. However, no current treatment is capable of significantly reducing HBsAg expression in patients. Our previous studies had confirmed the ability of CRISPR-Cas9 in disrupting HBV cccDNA. Here, to inhibit HBV expression efficiently in the mouse model of chronic HBV infection, the miniaturized CRISPR-SaCas9 system compatible with a HBV core region derived guide-RNA had been packaged in recombinant adeno-associated virus (AAV) type 8, which lowered the levels of serum HBsAg, HBeAg, and HBV DNA efficiently in HBV transgenic mice during 58 days continuous observation after vein injection. It further confirms the potential of the CRISPR-Cas9 technique for use in hepatitis B gene therapy. Frontiers Media S.A. 2018-09-11 /pmc/articles/PMC6141737/ /pubmed/30254645 http://dx.doi.org/10.3389/fimmu.2018.02080 Text en Copyright © 2018 Li, Sheng, Liu, Wang, Zhao, Yang, Jia, Li, Wang, Xie, Xu, Sun, Qiu and Song. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Li, Hao
Sheng, Chunyu
Liu, Hongbo
Wang, Shan
Zhao, Jiangyun
Yang, Lang
Jia, Leili
Li, Peng
Wang, Ligui
Xie, Jing
Xu, Dongping
Sun, Yansong
Qiu, Shaofu
Song, Hongbin
Inhibition of HBV Expression in HBV Transgenic Mice Using AAV-Delivered CRISPR-SaCas9
title Inhibition of HBV Expression in HBV Transgenic Mice Using AAV-Delivered CRISPR-SaCas9
title_full Inhibition of HBV Expression in HBV Transgenic Mice Using AAV-Delivered CRISPR-SaCas9
title_fullStr Inhibition of HBV Expression in HBV Transgenic Mice Using AAV-Delivered CRISPR-SaCas9
title_full_unstemmed Inhibition of HBV Expression in HBV Transgenic Mice Using AAV-Delivered CRISPR-SaCas9
title_short Inhibition of HBV Expression in HBV Transgenic Mice Using AAV-Delivered CRISPR-SaCas9
title_sort inhibition of hbv expression in hbv transgenic mice using aav-delivered crispr-sacas9
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141737/
https://www.ncbi.nlm.nih.gov/pubmed/30254645
http://dx.doi.org/10.3389/fimmu.2018.02080
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