title: Achieving HIV-1 Control through RNA-Directed Gene Regulation.
abstract: HIV-1 infection has been transformed by combined anti-retroviral therapy (ART), changing a universally fatal infection into a controllable infection. However, major obstacles for an HIV-1 cure exist. The HIV latent reservoir, which exists in resting CD4+ T cells, is not impacted by ART, and can reactivate when ART is interrupted or ceased. Additionally, multi-drug resistance can arise. One alternate approach to conventional HIV-1 drug treatment that is being explored involves gene therapies utilizing RNA-directed gene regulation. Commonly known as RNA interference (RNAi), short interfering RNA (siRNA) induce gene silencing in conserved biological pathways, which require a high degree of sequence specificity. This review will provide an overview of the silencing pathways, the current RNAi technologies being developed for HIV-1 gene therapy, current clinical trials, and the challenges faced in progressing these treatments into clinical trials.
authors.affiliation: Kirby Institute, The University of New South Wales, Sydney, NSW 2052, Australia. vklemm@kirby.unsw.edu.au.
authors.forename: Vera
authors.initials: V
authors.lastname: Klemm
authors.affiliation: Kirby Institute, The University of New South Wales, Sydney, NSW 2052, Australia. jmitchell@kirby.unsw.edu.au.
authors.forename: Jye
authors.initials: J
authors.lastname: Mitchell
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Parkville, Victoria 3010, Australia. christina.cortez@unimelb.edu.au.|Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia. christina.cortez@unimelb.edu.au.
authors.forename: Christina
authors.initials: C
authors.lastname: Cortez-Jugo
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Parkville, Victoria 3010, Australia. francesca.cavalieri@unimelb.edu.au.|Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia. francesca.cavalieri@unimelb.edu.au.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cavalieri
authors.affiliation: Calimmune Inc., Darlinghurst, NSW 2011, Australia. geoff.symonds@calimmuneinc.com.
authors.forename: Geoff
authors.initials: G
authors.lastname: Symonds
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Parkville, Victoria 3010, Australia. fcaruso@unimelb.edu.au.|Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia. fcaruso@unimelb.edu.au.
authors.forename: Frank
authors.initials: F
authors.lastname: Caruso
authors.affiliation: Kirby Institute, The University of New South Wales, Sydney, NSW 2052, Australia. akelleher@kirby.unsw.edu.au.
authors.forename: Anthony Dominic
authors.initials: AD
authors.lastname: Kelleher
authors.affiliation: Kirby Institute, The University of New South Wales, Sydney, NSW 2052, Australia. cahlenstiel@kirby.unsw.edu.au.
authors.forename: Chantelle
authors.initials: C
authors.lastname: Ahlenstiel
keywords: HIV-1; RNAi; clinical trials; gene therapy; transcriptional gene silencing