title: The CRISPR/Cas9 system inactivates latent HIV-1 proviral DNA.
abstract: BACKGROUND
  Highly active antiretroviral therapy (HAART) has transformed HIV-1 infection from a deadly disease to a manageable chronic illness, albeit does not provide a cure. The recently developed genome editing system called CRISPR/Cas9 offers a new tool to inactivate the integrated latent HIV-1 DNA and may serve as a new avenue toward cure.
  
  
  RESULTS
  We tested 10 sites in HIV-1 DNA that can be targeted by CRISPR/Cas9. The engineered CRISPR/Cas9 system was introduced into the JLat10.6 cells that are latently infected by HIV-1. The sequencing results showed that each target site in HIV-1 DNA was efficiently mutated by CRISPR/Cas9 with the target site in the second exon of Rev (called T10) exhibiting the highest degree of mutation. As a result, HIV-1 gene expression and virus production were significantly diminished with T10 causing a 20-fold reduction.
  
  
  CONCLUSIONS
  The CRISPR/Cas9 complex efficiently mutates and deactivates HIV-1 proviral DNA in latently infected Jurkat cells. Our results also revealed a highly efficient Cas9 target site within the second exon of Rev that represents a promising target to be further explored in the CRISPR/Cas9-based cure strategy.
authors: Weijun
authors: W
authors: Zhu
authors: Rongyue
authors: R
authors: Lei
authors: Yann
authors: Y
authors: Le Duff
authors: Jian
authors: J
authors: Li
authors: Fei
authors: F
authors: Guo
authors: Mark A
authors: MA
authors: Wainberg
authors: Chen
authors: C
authors: Liang
mesh_terms: D064113:CRISPR-Cas Systems; D004279:DNA, Viral / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D011533:Proviruses / Q000276:immunology* / Q000502:physiology; D038301:Virus Inactivation; D017735:Virus Latency
chemical_list: D004279:DNA, Viral