Personalized gene therapy locks out HIV, paving the way to control virus without antiretroviral drugs

Abstract

Introduction: Advances in adoptive immunotherapy have enabled gene therapy approaches to be tested in clinical trials that involve the transfer of engineered immune cells to specifically target HIV-infected cells or block HIV infection or transmission. Genetic editing through engineered targeted nucleases provides a method for producing cells that are permanently resistant to HIV.

Areas covered: Here, we discuss current and developing gene therapy approaches aimed to confer resistance to HIV infection at the cellular level by targeting viral or cellular elements, with a focus on gene editing strategies that target viral entry. Human gene therapy trials in HIV infection are reviewed.

Expert opinion: In concept, a single infusion of genetically modified cells could potentially reduce the need for lifelong medication by providing long-term control over the virus (functional immunity). While the dream of completely eliminating viral reservoirs (sterilizing immunity) is appealing, this presents a significant additional hurdle and may not be necessary to improve long-term health. A single infusion, or a small number of infusions, of engineered cells may be shown in confirmatory clinical trials to produce a meaningful biologic effect. These techniques have implications for targeted gene therapy in HIV and other diseases.

Keywords:

• CCR5
• gene therapy
• genome editing
• HIV
• immunotherapy
• zinc finger nucleases

Acknowledgements

We would like to thank C June, P Tebas, J Riley and our late colleague R Carroll for advice and mentorship. Space restrictions precluded citing all relevant studies; however, we would like to acknowledge the contributions of all gene therapy and HIV researchers who have advanced research and clinical investigation.

Declaration of interest

This work was supported in part by NIAID Program Project Grant U19 AI066290, by the Penn Center for AIDS Research (P30 AIO4), by Sangamo BioSciences and by discretionary funds held by Dr Levine at the University of Pennsylvania. 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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