title: Disruption or Excision of Provirus as an Approach to HIV Cure.
abstract: An effective approach to HIV cure will almost certainly require a combination of strategies, including some means of reducing the latent HIV reservoir. Because the integrated HIV provirus represents the major source of viral persistence and reactivation, one attractive approach is the direct targeting of provirus for disruption or excision using targeted endonucleases, such as CRISPR/Cas9, zinc finger nucleases, TAL effector nucleases, or meganucleases (homing endonucleases). This article highlights some of the challenges for successful endonuclease therapy for HIV, including optimization of enzyme activity and specificity, the possible emergence of viral resistance, and most importantly, efficient in vivo delivery of the enzymes to a sufficient portion of the latent reservoir.
authors.affiliation: 1 Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle, Washington.|2 Virology Division, Department of Laboratory Medicine, University of Washington , Seattle, Washington.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Jerome
mesh_terms: D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D004279:DNA, Viral / Q000235:genetics; D004720:Endonucleases / Q000378:metabolism*; D015316:Genetic Therapy / Q000379:methods*; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D011533:Proviruses; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D004279:DNA, Viral; D004720:Endonucleases
keywords: CRISPR/Cas9; HIV cure; endonuclease; gene editing; gene therapy; provirus