The therapeutic application of CRISPR/Cas9 technologies for HIV

Abstract

Introduction: The use of antiretroviral therapy has led to a significant decrease in morbidity and mortality in HIV-infected individuals. Nevertheless, gene-based therapies represent a promising therapeutic paradigm for HIV-1, as they have the potential for sustained viral inhibition and reduced treatment interventions. One new method amendable to a gene-based therapy is the clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein-9 nuclease (Cas9) gene editing system.

Areas covered: CRISPR/Cas9 can be engineered to successfully modulate an array of disease-causing genetic elements. We discuss the diverse roles that CRISPR/Cas9 may play in targeting HIV and eradicating infection. The Cas9 nuclease coupled with one or more small guide RNAs can target the provirus to mediate excision of the integrated viral genome. Moreover, a modified nuclease-deficient Cas9 fused to transcription activation domains may induce targeted activation of proviral gene expression allowing for the purging of the latent reservoirs. These technologies can also be exploited to target host dependency factors such as the co-receptor CCR5, thus preventing cellular entry of the virus.

Expert opinion: The diversity of the CRISPR/Cas9 technologies offers great promise for targeting different stages of the viral life cycle, and have the capacity for mediating an effective and sustained genetic therapy against HIV.

Keywords:

• CRISPR/Cas9
• gene activation
• gene editing
• gene excision
• HIV-1
• latency
• RNA therapy

Acknowledgments

We thank members of the Weinberg and Morris laboratories for helpful discussion. S Saayman and SA Ali contributed equally to this work.

Declaration of interest

MS Weinberg is supported by funding from the South African Medical Research Council (MRC), and National Research Foundation (NRF). He has received grants for materials/supplies/salaries from the NIH. KV Morris is supported by NIAID PO1 AI099783-01 and has received grants for materials/supplies/salaries from the NIH. SA Ali is supported on a research fellowship from the MRC of South Africa. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Notes

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