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Gene Therapy Blueprints for NeuroAIDS

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Global Virology II - HIV and NeuroAIDS

Abstract

Since the start of the HIV/AIDS pandemic, 37 years ago, early work produced evidence for CNS involvement and that HIV-1B infection could penetrate the brain. Since then, a plethora of studies further identified many host proteins, RNAs, and genes implicated in brain involvement consequent to HIV-1B infection. This chapter summarizes the various types of gene therapy platforms available in recent years for neuroAIDS. This is both important and complex and should be validated meticulously to reduce the risk of malfunction of genes and network pathways other than those under the specific molecular treatments intended. Consequently, we describe several of the genes known to be involved in neuroAIDS for potential application for various techniques of gene therapy. With more than 179,962 publications using gene therapy, as of February 27, 2017, where are all the clinically appropriate products applying all this knowledge? Ethical considerations of gene modification are discussed as well.

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Notes

  1. 1.

    Interacting genes and proteins can compose genetic circuits. These can empower cells to individually counter environmental and signal inputs. Moreover, communication and decision-making can ensue.

  2. 2.

    Inteins are protein introns, parts of proteins that self-excise analogously to DNA genome and messenger RNA introns. Inteins were discovered decades ago and have resurfaced as a twenty-first-century bioengineering tool.

  3. 3.

    PM1 cells are a human T-cell line, which has exceptional susceptibility to infection by primary HIV-1 isolates.

  4. 4.

    A review of the presence of numerous cytokine and chemokine mediators of neuroinflammation and neurodegeneration includes HIV encephalitis among other inflammatory diseases [103].

  5. 5.

    Electroporation induces pores in cell membranes using controlled electrical pulses [197].

  6. 6.

    The melittin 26-amino sequence oligopeptide is GIGAVLKVLTTGLPALISWIKRKRQQ. Melittin disrupts the HIV envelope by inducing holes [216].

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Authors and Affiliations

  1. Trinity School of Medicine, MS4, 5575 North Point Parkway Suite 230, Alpharetta, GA, 30022, USA

    Hector E. Rodriguez ThM, MD

  2. Division of Infectious Diseases and International Health, Department of Internal Medicine, University of South Florida, Morsani College of Medicine, Tampa, FL, 33606, USA

    Seetha Lakshmi MD, Charurut Somboonwit MD, Anteneh Addisu MD, PhD, Louise Gutierrez MD, John T. Sinnott MD & Paul Shapshak PhD

  3. Division of General Internal Medicine, Department of Internal Medicine, University of South Florida, Morsani College of Medicine, Tampa, FL, 33612, USA

    Asa Oxner MD, Lucy Guerra MD & John T. Sinnott MD

  4. Biomedical Informatics, #9, Irulan Sandy Annex, Puducherry, Puducherry State, 607402, India

    Christina Nilofer MS & Pandjassarame Kangueane PhD

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  1. Department of Internal Medicine, Division of Infectious Diseases and International Health, University of South Florida, Tampa, Florida, USA

    Paul Shapshak

  2. Department of Neurology, UCLA David Geffen School of Medicine, Los Angeles, California, USA

    Andrew J. Levine

  3. Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico, USA

    Brian T. Foley

  4. Department of Internal Medicine, Division of Infectious Diseases and International Health, University of South Florida, Morsani College of Medicine, Tampa, Florida, USA

    Charurut Somboonwit

  5. Department of Neurology, UCLA David Geffen School of Medicine, Los Angeles, California, USA

    Elyse Singer

  6. Department of Oral Biology and Medicine, UCLA School of Dentistry, Los Angeles, California, USA

    Francesco Chiappelli

  7. Department of Internal Medicine, Division of Infectious Diseases and International Health, University of South Florida, Morsani College of Medicine, Tampa, Florida, USA

    John T. Sinnott

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Rodriguez, H.E. et al. (2017). Gene Therapy Blueprints for NeuroAIDS. In: Shapshak, P., et al. Global Virology II - HIV and NeuroAIDS. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7290-6_37

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