Specific Reactivation of Latent HIV-1 by dCas9-SunTag-VP64-mediated Guide RNA Targeting the HIV-1 Promoter

Molecular Therapy : the Journal of the American Society of Gene Therapy
Haiyan JiHuanzhang Zhu

Abstract

HIV-1 escapes antiretroviral agents by integrating into the host DNA and forming a latent transcriptionally silent HIV-1 provirus. Transcriptional activation is prerequisite for reactivation and the eradication of latent HIV-1 proviruses. dCas9-SunTag-VP64 transcriptional system has been reported that it can robustly activate the expression of an endogenous gene using a single guide RNA (sgRNA). Here, we systematically investigated the potential of dCas9-SunTag-VP64 with the designed sgRNAs for reactivating latent HIV-1. We found dCas9-SunTag-VP64 with sgRNA 4 or sgRNA 5 targeted from -164 to -146 or -124 to -106 bp upstream of the transcription start sites of HIV-1 could induce high expression of luciferase reporter gene after screening of sgRNAs targeting different regions of the HIV-1 promoter. Further, we confirmed that dCas9-SunTag-VP64 with sgRNA 4 or sgRNA 5 can effectively reactivate latent HIV-1 transcription in several latently infected human T-cell lines. Moreover, we confirmed that the reactivation of latent HIV-1 by dCas9-SunTag-VP64 with the designed sgRNA occurred through specific binding to the HIV-1 LTR promoter without genotoxicity and global T-cell activation. Taken together, our data demonstrated dCas9-SunTa...Continue Reading

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Citations

Mar 10, 2016·Molecular Therapy : the Journal of the American Society of Gene Therapy·Angel Lin, Zachary Klase
Jan 18, 2018·Viruses·Shuliang ChenDeyin Guo
Nov 2, 2017·Expert Review of Anti-infective Therapy·Marta TrevisanLuisa Barzon
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Apr 10, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Choongho Lee
Dec 6, 2019·International Journal of Molecular Sciences·Sergey BrezginVladimir Chulanov
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Mar 1, 2018·ACS Synthetic Biology·Nhung Thi NguyenYubin Zhou

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