title: TALEN gene editing takes aim on HIV.
abstract: Transcription activator-like effector nucleases (TALENs) are one of several types of programmable, engineered nucleases that bind and cleave specific DNA sequences. Cellular machinery repairs the cleaved DNA by introducing indels. In this review, we emphasize the potential, explore progress, and identify challenges in using TALENs as a therapeutic tool to treat HIV infection. TALENs have less off-target editing and can be more effective at tolerating HIV escape mutations than CRISPR/Cas-9. Scientists have explored TALEN-mediated editing of host genes such as viral entry receptors (CCR5 and CXCR4) and a protein involved in proviral integration (LEDGF/p75). Viral targets include the proviral DNA, particularly focused on the long terminal repeats. Major challenges with translating gene therapy from bench to bedside are improving cleavage efficiency and delivery, while minimizing off-target editing, cytotoxicity, and immunogenicity. However, rapid improvements in TALEN technology are enhancing cleavage efficiency and specificity. Therapeutic testing in animal models of HIV infection will help determine whether TALENs are a viable HIV treatment therapy. TALENs or other engineered nucleases could shift the therapeutic paradigm from life-long antiretroviral therapy toward eradication of HIV infection.
authors.affiliation: Nevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada, Las Vegas, NV, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Benjamin
authors.affiliation: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, USA.
authors.forename: Bradford K
authors.initials: BK
authors.lastname: Berges
authors.affiliation: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Solis-Leal
authors.affiliation: Nevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada, Las Vegas, NV, USA.
authors.forename: Omoyemwen
authors.initials: O
authors.lastname: Igbinedion
authors.affiliation: Nevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada, Las Vegas, NV, USA.
authors.forename: Christy L
authors.initials: CL
authors.lastname: Strong
authors.affiliation: Nevada Institute of Personalized Medicine and School of Life Sciences, University of Nevada, Las Vegas, NV, USA. martin.schiller@unlv.edu.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Schiller
mesh_terms: D001483:Base Sequence; D000072669:Gene Editing; D015658:HIV Infections / Q000628:therapy*; D006801:Humans; D012689:Sequence Homology, Nucleic Acid; D000069896:Transcription Activator-Like Effector Nucleases
chemical_list: D000069896:Transcription Activator-Like Effector Nucleases