title: Genome editing strategies: potential tools for eradicating HIV-1/AIDS.
abstract: Current therapy for controlling human immunodeficiency virus (HIV-1) infection and preventing acquired immunodeficiency syndrome (AIDS) progression has profoundly decreased viral replication in cells susceptible to HIV-1 infection, but it does not eliminate the low level of viral replication in latently infected cells, which contain integrated copies of HIV-1 proviral DNA. There is an urgent need for the development of HIV-1 genome eradication strategies that will lead to a permanent or "sterile" cure of HIV-1/AIDS. In the past few years, novel nuclease-initiated genome editing tools have been developing rapidly, including zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the CRISPR/Cas9 system. These surgical knives, which can excise any genome, provide a great opportunity to eradicate the HIV-1 genome by targeting highly conserved regions of the HIV-1 long terminal repeats or essential viral genes. Given the time consuming and costly engineering of target-specific ZFNs and TALENs, the RNA-guided endonuclease Cas9 technology has emerged as a simpler and more versatile technology to allow permanent removal of integrated HIV-1 proviral DNA in eukaryotic cells, and hopefully animal models or human patients. The major unmet challenges of this approach at present include inefficient nuclease gene delivery, potential off-target cleavage, and cell-specific genome targeting. Nanoparticle or lentivirus-mediated delivery of next generation Cas9 technologies including nickase or RNA-guided FokI nuclease (RFN) will further improve the potential for genome editing to become a promising approach for curing HIV-1/AIDS.
authors.affiliation: Department of Neuroscience, Center for Neurovirology and the Comprehensive NeuroAIDS Center, Temple University School of Medicine, Philadelphia, PA, 19140, USA, kamel.khalili@temple.edu.
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
authors.forename: Rafal
authors.initials: R
authors.lastname: Kaminski
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gordon
authors.forename: Laura
authors.initials: L
authors.lastname: Cosentino
authors.forename: Wenhui
authors.initials: W
authors.lastname: Hu
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy*; D000818:Animals; D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D015316:Genetic Therapy / Q000379:methods; D016679:Genome, Viral; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D012367:RNA, Viral / Q000187:drug effects; D012260:Ribonucleases / Q000494:pharmacology*
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral; D012260:Ribonucleases