文章基本信息

标题：RNA-guided endonuclease provides a therapeutic strategy to cure latent herpesviridae infection
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作者：Jianbin Wang ; Stephen R. Quake
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2014
卷号：111
期号：36
页码：13157-13162
DOI：10.1073/pnas.1410785111
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceLatent viral infection is a major obstacle for effective antiviral treatment and presents a continuous risk to the host. The dormant viral genome during latent infection provides few therapeutic targets other than itself for antiviral drug development. This study demonstrates the clearance of latent Epstein-Barr virus genomes in a subpopulation of Burkitt's lymphoma patient-derived cells with clustered regularly interspaced short palindromic repeat/Cas9 nuclease. Viral genome destruction leads to proliferation arrest and apoptosis in Epstein-Barr virus-infected cells, with no observed cytotoxicity to noninfected cells. Although many hurdles remain before this approach could be used in the clinic, this strategy may lead to a generalized approach to cure latent viral infections. Latent viral infection is a persistent cause of human disease. Although standard antiviral therapies can suppress active viral replication, no existing treatment can effectively eradicate latent infection and therefore a cure is lacking for many prevalent viral diseases. The prokaryotic immune system clustered regularly interspaced short palindromic repeat (CRISPR)/Cas evolved as a natural response to phage infections, and we demonstrate here that the CRISPR/Cas9 system can be adapted for antiviral treatment in human cells by specifically targeting the genomes of latent viral infections. Patient-derived cells from a Burkitt's lymphoma with latent Epstein-Barr virus infection showed dramatic proliferation arrest and a concomitant decrease in viral load after exposure to a CRISPR/Cas9 vector targeted to the viral genome.
关键词：genome editing ; latency ; herpes virus