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

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.