Gene Therapy Approaches to Human Immunodeficiency Virus and Other Infectious Diseases

Advances in gene therapy technologies, particularly in gene editing, are suggesting new avenues for the treatment of human immunodeficiency virus and other infectious diseases. This article outlines recent developments in antiviral gene therapies, including those based on the disruption of entry receptors or that target viral genomes using targeted nucleases, such as the CRISPR/Cas9 system. In addition, new ways to express circulating antiviral factors, such as antibodies, and approaches to harness and engineer the immune system to provide an antiviral effect that is not naturally achieved are described.

Key points

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Recent innovations and clinical successes in gene therapy have provided the impetus to apply these techniques toward the treatment of infectious diseases, particularly human immunodeficiency virus (HIV).
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One significant gene therapy for HIV currently in translation involves the use of zinc finger nucleases to disrupt the HIV coreceptor CCR5, rendering T cells resistant to HIV infection.
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Targeted nucleases are being developed to disrupt or excise proviral DNA in HIV and hepatitis B virus infection, directly targeting latent viral reservoirs that are invisible to the immune system.
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Gene transfer using adeno-associated virus vectors allows systemic expression of broadly neutralizing antibodies against HIV, influenza, and respiratory syncytial virus, representing an approach for long-lived passive immunization.
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Gene therapy also allows for combinatorial approaches, targeting multiple aspects of a pathogen, and potentially paving the path toward long-term suppression or cure for HIV and other pernicious infections.