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A combinational CRISPR/Cas9 gene-editing approach can halt HIV replication and prevent viral escape.

HIV presents one of the highest evolutionary rates ever detected and combination antiretroviral therapy is needed to overcome the plasticity of the virus population and control viral replication. Conventional treatments lack the ability to clear the latent reservoir, which remains the major obstacle... Full description

Journal Title: Scientific reports February 8, 2017, Vol.7, p.41968
Main Author: Lebbink, Robert Jan
Other Authors: de Jong, Dorien C M , Wolters, Femke , Kruse, Elisabeth M , van Ham, Petra M , Wiertz, Emmanuel J H J , Nijhuis, Monique
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 2045-2322 ; DOI: 10.1038/srep41968
Link: http://search.proquest.com/docview/1866295638/?pq-origsite=primo
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recordid: proquest1866295638
title: A combinational CRISPR/Cas9 gene-editing approach can halt HIV replication and prevent viral escape.
format: Article
creator:
  • Lebbink, Robert Jan
  • de Jong, Dorien C M
  • Wolters, Femke
  • Kruse, Elisabeth M
  • van Ham, Petra M
  • Wiertz, Emmanuel J H J
  • Nijhuis, Monique
subjects:
  • Crispr-Cas Systems–Methods
  • Gene Editing–Therapy
  • Gene Targeting–Virology
  • Genome, Viral–Genetics
  • Hek293 Cells–Genetics
  • HIV Infections–Genetics
  • HIV-1–Genetics
  • Humans–Genetics
  • Jurkat Cells–Genetics
  • RNA, Guide–Genetics
  • Virus Replication–Genetics
  • RNA, Guide
ispartof: Scientific reports, February 8, 2017, Vol.7, p.41968
description: HIV presents one of the highest evolutionary rates ever detected and combination antiretroviral therapy is needed to overcome the plasticity of the virus population and control viral replication. Conventional treatments lack the ability to clear the latent reservoir, which remains the major obstacle towards a cure. Novel strategies, such as CRISPR/Cas9 gRNA-based genome-editing, can permanently disrupt the HIV genome. However, HIV genome-editing may accelerate viral escape, questioning the feasibility of the approach. Here, we demonstrate that CRISPR/Cas9 targeting of single HIV loci, only partially inhibits HIV replication and facilitates rapid viral escape at the target site. A combinatorial approach of two strong gRNAs targeting different regions of the HIV genome can completely abrogate viral replication and prevent viral escape. Our data shows that the accelerating effect of gene-editing on viral escape can be overcome and as such gene-editing may provide a future alternative for control of HIV-infection.
language: eng
source:
identifier: E-ISSN: 2045-2322 ; DOI: 10.1038/srep41968
fulltext: fulltext
issn:
  • 20452322
  • 2045-2322
url: Link


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titleA combinational CRISPR/Cas9 gene-editing approach can halt HIV replication and prevent viral escape.
creatorLebbink, Robert Jan ; de Jong, Dorien C M ; Wolters, Femke ; Kruse, Elisabeth M ; van Ham, Petra M ; Wiertz, Emmanuel J H J ; Nijhuis, Monique
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ispartofScientific reports, February 8, 2017, Vol.7, p.41968
identifierE-ISSN: 2045-2322 ; DOI: 10.1038/srep41968
subjectCrispr-Cas Systems–Methods ; Gene Editing–Therapy ; Gene Targeting–Virology ; Genome, Viral–Genetics ; Hek293 Cells–Genetics ; HIV Infections–Genetics ; HIV-1–Genetics ; Humans–Genetics ; Jurkat Cells–Genetics ; RNA, Guide–Genetics ; Virus Replication–Genetics ; RNA, Guide
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descriptionHIV presents one of the highest evolutionary rates ever detected and combination antiretroviral therapy is needed to overcome the plasticity of the virus population and control viral replication. Conventional treatments lack the ability to clear the latent reservoir, which remains the major obstacle towards a cure. Novel strategies, such as CRISPR/Cas9 gRNA-based genome-editing, can permanently disrupt the HIV genome. However, HIV genome-editing may accelerate viral escape, questioning the feasibility of the approach. Here, we demonstrate that CRISPR/Cas9 targeting of single HIV loci, only partially inhibits HIV replication and facilitates rapid viral escape at the target site. A combinatorial approach of two strong gRNAs targeting different regions of the HIV genome can completely abrogate viral replication and prevent viral escape. Our data shows that the accelerating effect of gene-editing on viral escape can be overcome and as such gene-editing may provide a future alternative for control of HIV-infection.
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date2017-02-08