NDLI: Suppression of hepatitis B virus DNA accumulation in chronically infected cells using a bacterial CRISPR/Cas RNA-guided DNA endonuclease

Content Provider	PubMed Central
Author	Kennedy, Edward M. Bassit, Leda C. Mueller, Henrik Kornepati, Anand V. R. Bogerd, Hal P. Nie, Ting Chatterjee, Payel Hassan, Javanbakht Schinazi, Raymond F. Cullen, Bryan R.
Copyright Year	2014
Abstract	Hepatitis B virus (HBV) remains a major human pathogen, with over 240 million individuals suffering from chronic HBV infections. These can persist for decades due to the lack of therapies that can effectively target the stable viral covalently closed circular (ccc) DNA molecules present in infected hepatocytes. Using lentiviral transduction of a bacterial Cas9 gene and single guide RNAs (sgRNAs) specific for HBV, we observed effective inhibition of HBV DNA production in in vitro models of both chronic and de novo HBV infection. Cas9/sgRNA combinations specific for HBV reduced total viral DNA levels by up to ~1000-fold and HBV cccDNA levels by up to ~10-fold and also mutationally inactivated the majority of the residual viral DNA. Together, these data provide proof of principle for the hypothesis that CRISPR/Cas systems have the potential to serve as effective tools for the depletion of the cccDNA pool in chronically HBV infected individuals.
Related Links	http://dx.doi.org/10.1016/j.virol.2014.12.001
Ending Page	205
Page Count	10
Starting Page	196
File Format	PDF
ISSN	00426822
e-ISSN	10960341
Journal	Virology
Volume Number	476
Language	English
Publisher Date	2015-02-01
Access Restriction	Open
Subject Keyword	Virology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Virology

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