Fight fire with fire: Gene therapy strategies to cure HIV

ABSTRACT

Introduction: Human Immunodeficiency Virus (HIV) to date remains one of the most notorious viruses mankind has ever faced. Despite enormous investments in HIV research for more than 30 years an effective cure for HIV has been elusive.

Areas covered: Combination antiretroviral therapy (cART) suppresses active viral replication, but is not able to eliminate the virus completely due to stable integration of HIV inside the host genome of infected cells and the establishment of a latent reservoir, that is insensitive to cART. Nevertheless, this latent HIV reservoir is fully capable to refuel viral replication when treatment is stopped, creating a major obstacle towards a cure for HIV. Several gene therapy approaches ranging from the generation of HIV resistant CD4 + T cells to the eradication of HIV infected cells by immune cell engineering are currently under pre-clinical and clinical investigation and may present a promising road to a cure. In this review, we focus on the status and the prospects of gene therapy strategies to cure/eradicate HIV.

Expert commentary: Recent advances in gene therapy for oncology and infectious diseases indicate that gene therapy may be a feasible and very potent cure strategy, and therefore a potential game changer in the search for an effective HIV cure.

KEYWORDS:

• Artificial TCRs
• broadly neutralizing antibodies
• CAR T cells
• chimeric antigen receptors
• CCR5 knockout
• CRISPR-Cas9
• gene therapy
• hematopoietic stem cells
• HIV cure
• latency
• shock and kill
• vectored immunoprophylaxis
• zinc finger nucleases

Declaration of interest

J Huyghe is supported by the Ghent university Special Research Fund through a doctoral scholarship (BOF16/DOC/317). L Vandekerckhove is a Senior Clinical Investigator funded by the Research Foundation Flanders (FWO 1.8.020.09. N.00). M Sips is supported by HIV Ontrafelen Fund. 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 apart from those disclosed.

Additional information

Funding

This publication has been made possible by the Ghent University Special Research Fund through Jon Huyghe’s doctoral scholarship (BOF16/DOC/317), Magdalena Sips is supported by HIV Ontrafelen Fund and the Research Foundation Flanders (FWO) grant is attributed to Linos Vandekerckhove (FWO 1.8.020.09. N.00).