Achieving HIV-1 Control through RNA-Directed Gene Regulation

Vera Klemm; Jye Mitchell; Christina Cortez-Jugo; Francesca Cavalieri; Geoff Symonds; Frank Caruso; Anthony Dominic Kelleher; Chantelle Ahlenstiel

doi:10.3390/genes7120119

Achieving HIV-1 Control through RNA-Directed Gene Regulation

Genes (Basel). 2016 Dec 7;7(12):119. doi: 10.3390/genes7120119.

Authors

Vera Klemm¹, Jye Mitchell², Christina Cortez-Jugo^{3

4}, Francesca Cavalieri^{5

6}, Geoff Symonds⁷, Frank Caruso^{8

9}, Anthony Dominic Kelleher¹⁰, Chantelle Ahlenstiel¹¹

Affiliations

¹ Kirby Institute, The University of New South Wales, Sydney, NSW 2052, Australia. vklemm@kirby.unsw.edu.au.
² Kirby Institute, The University of New South Wales, Sydney, NSW 2052, Australia. jmitchell@kirby.unsw.edu.au.
³ ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Parkville, Victoria 3010, Australia. christina.cortez@unimelb.edu.au.
⁴ Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia. christina.cortez@unimelb.edu.au.
⁵ ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Parkville, Victoria 3010, Australia. francesca.cavalieri@unimelb.edu.au.
⁶ Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia. francesca.cavalieri@unimelb.edu.au.
⁷ Calimmune Inc., Darlinghurst, NSW 2011, Australia. geoff.symonds@calimmuneinc.com.
⁸ ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Parkville, Victoria 3010, Australia. fcaruso@unimelb.edu.au.
⁹ Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia. fcaruso@unimelb.edu.au.
¹⁰ Kirby Institute, The University of New South Wales, Sydney, NSW 2052, Australia. akelleher@kirby.unsw.edu.au.
¹¹ Kirby Institute, The University of New South Wales, Sydney, NSW 2052, Australia. cahlenstiel@kirby.unsw.edu.au.

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.

Keywords: HIV-1; RNAi; clinical trials; gene therapy; transcriptional gene silencing.

Publication types

Review