Targeted DNA Mutagenesis for the Cure of Chronic Viral Infections

StephenW

http://jvi.asm.org/content/86/17/8920.abstract?etoc
Targeted DNA Mutagenesis for the Cure of Chronic Viral Infections                                 

• Joshua T. Schiffera,b,
• Martine Auberta,
• Nicholas D. Webera,c,
• Esther Mintzera,d,
• Daniel Stonea and
• Keith R. Jeromea,c
  

- Author Affiliations

                  

• aFred Hutchinson Cancer Research Center, Vaccine and Infectious Diseases Division, Seattle, Washington, USA
• bDepartment of Medicine, University of Washington, Seattle, Seattle, Washington, USA
• cDepartment of Laboratory Medicine, University of Washington, Seattle, Seattle, Washington, USA
• dDepartment of Microbiology, University of Washington, Seattle, Seattle, Washington, USA
  

               

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV), and herpes simplex virus (HSV) have been incurable to date because effective antiviral therapies target only replicating viruses and do not eradicate latently integrated or nonreplicating episomal viral genomes. Endonucleases that can target and cleave critical regions within latent viral genomes are currently in development. These enzymes are being engineered with high specificity such that off-target binding of cellular DNA will be absent or minimal. Imprecise nonhomologous-end-joining (NHEJ) DNA repair following repeated cleavage at the same critical site may permanently disrupt translation of essential viral proteins. We discuss the benefits and drawbacks of three types of DNA cleavage enzymes (zinc finger endonucleases, transcription activator-like [TAL] effector nucleases [TALENs], and homing endonucleases [also called meganucleases]), the development of delivery vectors for these enzymes, and potential obstacles for successful treatment of chronic viral infections. We then review issues regarding persistence of HIV-1, HBV, and HSV that are relevant to eradication with genome-altering approaches.
FOOTNOTES           

            

• Address correspondence to Keith R. Jerome, [email protected].
  

StephenW

有针对性的治疗慢性病毒感染的DNA突变

    约书亚T. Schiffera，B，
    马丁Auberta
    尼古拉斯·D. Webera，C，
    以斯帖Mintzera，D，
    丹尼尔Stonea和
    基斯河Jeromea，C

- 作者背景

    aFred哈钦森癌症研究中心疫苗和传染病科，西雅图，华盛顿，美国
    bDepartment的医学院，华盛顿大学，西雅图，西雅图，华盛顿，美国
    cDepartment的医学实验室，华盛顿大学，西雅图，华盛顿，西雅图，美国
    dDepartment的微生物，华盛顿大学，西雅图，西雅图，华盛顿，美国

摘要

人类免疫缺陷病毒1型（HIV-1），B型肝炎病毒（HBV），单纯疱疹病毒（HSV）的最新不治之症，因为有效的抗病毒治疗的目标只有复制的病毒和不铲除的潜伏集成或nonreplicating送入胞病毒基因组。目前正在开发中的内切酶，可以针对关键区域内潜伏的病毒基因组的切割。这些酶工程等具有高特异性脱靶细胞的DNA结合，将缺席或最小。不精确的非同源年底加入（NHEJ能）DNA修复重复相同的关键部位的断裂后，可能会永久破坏重要的病毒蛋白的翻译。我们将讨论三种类型的DNA切割酶的优点和缺点（锌指核酸内切酶，转录激活，如[鲎]效应核酸塔伦斯也称为meganucleases]）]，归巢内切酶，这些酶的载体的发展，成功治疗慢性病毒感染的潜在障碍。然后，我们检讨有关的问题，乙肝病毒HIV-1和HSV的持久性有关改变基因的方法来根除。
脚注

    通讯地址以基思·杰罗姆，[email protected]。

咬牙硬挺

这个消息牛啊！直捣黄龙的方法！关注。还有啊rep的消息有了吗？