title: The therapeutic application of CRISPR/Cas9 technologies for HIV.
abstract: BACKGROUND
  The use of antiretroviral therapy has led to a significant decrease in morbidity and mortality in HIV-infected individuals. Nevertheless, gene-based therapies represent a promising therapeutic paradigm for HIV-1, as they have the potential for sustained viral inhibition and reduced treatment interventions. One new method amendable to a gene-based therapy is the clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein-9 nuclease (Cas9) gene editing system.
  
  
  METHODS
  CRISPR/Cas9 can be engineered to successfully modulate an array of disease-causing genetic elements. We discuss the diverse roles that CRISPR/Cas9 may play in targeting HIV and eradicating infection. The Cas9 nuclease coupled with one or more small guide RNAs can target the provirus to mediate excision of the integrated viral genome. Moreover, a modified nuclease-deficient Cas9 fused to transcription activation domains may induce targeted activation of proviral gene expression allowing for the purging of the latent reservoirs. These technologies can also be exploited to target host dependency factors such as the co-receptor CCR5, thus preventing cellular entry of the virus.
  
  
  CONCLUSIONS
  The diversity of the CRISPR/Cas9 technologies offers great promise for targeting different stages of the viral life cycle, and have the capacity for mediating an effective and sustained genetic therapy against HIV.
authors: The Scripps Research Institute, Department of Molecular and Experimental Medicine , 10550 North Torrey Pines Road, La Jolla, CA, 92037 , USA.
authors: Sheena
authors: S
authors: Saayman
authors: Stuart A
authors: SA
authors: Ali
authors: Kevin V
authors: KV
authors: Morris
authors: Marc S
authors: MS
authors: Weinberg
mesh_terms: D000818:Animals; D064130:CRISPR-Associated Proteins / Q000235:genetics / Q000627:therapeutic use*; D064112:Clustered Regularly Interspaced Short Palindromic Repeats / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods / Q000639:trends*; D015658:HIV Infections / Q000235:genetics* / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics; D006801:Humans
chemical_list: D064130:CRISPR-Associated Proteins
keywords: CRISPR/Cas9; HIV-1; RNA therapy; gene activation; gene editing; gene excision; latency