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Novel AIDS therapies based on gene editing

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Abstract

HIV/AIDS remains a major public health issue. In 2014, it was estimated that 36.9 million people are living with HIV worldwide, including 2.6 million children. Since the advent of combination antiretroviral therapy (cART), in the 1990s, treatment has been so successful that in many parts of the world, HIV has become a chronic condition in which progression to AIDS has become increasingly rare. However, while people with HIV can expect to live a normal life span with cART, lifelong medication is required and cardiovascular, renal, liver, and neurologic diseases are still possible, which continues to prompt research for a cure for HIV. Infected reservoir cells, such as CD4+ T cells and myeloid cells, allow persistence of HIV as an integrated DNA provirus and serve as a potential source for the re-emergence of virus. Attempts to eradicate HIV from these cells have focused mainly on the so-called “shock and kill” approach, where cellular reactivation is induced so as to trigger the purging of virus-producing cells by cytolysis or immune attack. This approach has several limitations and its usefulness in clinical applications remains to be assessed. Recent advances in gene-editing technology have allowed the use of this approach for inactivating integrated proviral DNA in the genome of latently infected cells or knocking out HIV receptors. Here, we review this strategy and its potential to eliminate the latent HIV reservoir resulting in a sterile cure of AIDS.

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Acknowledgements

We thank the past and present members of the Department of Neuroscience for their continued support and insightful discussions. We also acknowledge the intellectual contributions of the Katz School of Medicine at Temple University Comprehensive NeuroAIDS Center (Basic Science Cores I and II) (NIH P30MH092177). We are grateful to Cynthia Papaleo for editorial assistance.

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Authors and Affiliations

  1. Department of Neuroscience, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor, Philadelphia, PA, 19140, USA

    Kamel Khalili, Martyn K. White & Jeffrey M. Jacobson

  2. Center for Neurovirology and Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor, Philadelphia, PA, 19140, USA

    Kamel Khalili, Martyn K. White & Jeffrey M. Jacobson

  3. Center for Translational AIDS Research, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor, Philadelphia, PA, 19140, USA

    Kamel Khalili & Jeffrey M. Jacobson

  4. Department of Medicine, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor, Philadelphia, PA, 19140, USA

    Jeffrey M. Jacobson

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Khalili, K., White, M.K. & Jacobson, J.M. Novel AIDS therapies based on gene editing. Cell. Mol. Life Sci. 74, 2439–2450 (2017). https://doi.org/10.1007/s00018-017-2479-z

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