Suppression of hepatitis B virus DNA accumulation in chronically infected cells using a bacterial CRISPR/Cas RNA-guided DNA endonuclease.
Suppression of hepatitis B virus DNA accumulation in chronically infected cells using a bacterial CRISPR/Cas RNA-guided DNA endonuclease.
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DOI：
10.1016/j.virol.2014.12.001
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发表时间：
2015-02
期刊：
影响因子：
3.7
通讯作者：
Cullen, Bryan R.
中科院分区：
文献类型：
--
作者：
Kennedy, Edward M.;Bassit, Leda C.;Mueller, Henrik;Kornepati, Anand V. R.;Bogerd, Hal P.;Nie, Ting;Chatterjee, Payel;Javanbakht, Hassan;Schinazi, Raymond F.;Cullen, Bryan R.
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.
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影响因子：
64.5
作者：
Yang H;Wang H;Shivalila CS;Cheng AW;Shi L;Jaenisch R
通讯作者：
Jaenisch R
DOI：
10.1038/mtna.2014.38
发表时间：
2014-08-19
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
Hsu PD;Lander ES;Zhang F
通讯作者：
Zhang F
影响因子：
4.9
作者：
Ladner, SK;Otto, MJ;King, RW
通讯作者：
King, RW
DOI：
10.1073/pnas.84.4.1005
发表时间：
1987-02-01
影响因子：
11.1
作者：
SELLS, MA;CHEN, ML;ACS, G
通讯作者：
ACS, G