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Stem Cell Gene Therapy for HIV: Strategies to Inhibit Viral Entry and Replication

  • HIV Pathogenesis and Treatment (AL Landay, Section Editor)
  • Published:
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Abstract

Since the demonstration of a cure of an HIV+ patient with an allogeneic stem cell transplant using naturally HIV-resistant cells, significant interest in creating similar autologous products has fueled the development of a variety of “cell engineering” approaches to stem cell therapy for HIV. Among the more well-studied strategies is the inhibition of viral entry through disruption of expression of viral co-receptors or through competitive inhibitors of viral fusion with the cell membrane. Preclinical evaluation of these approaches often starts in vitro but ultimately is tested in animal models prior to clinical implementation. In this review, we trace the development of several key approaches (meganucleases, short hairpin RNA (shRNA), and fusion inhibitors) to modification of hematopoietic stem cells designed to impart resistance to HIV to their T-cell and monocytic progeny. The basic evolution of technologies through in vitro and in vivo testing is discussed as well as the pros and cons of each approach and how the addition of postentry inhibitors may enhance the overall antiviral efficacy of these approaches.

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Acknowledgments

The author would like to thank Ms. Nancy Gonzalez for her help in preparing Table 1 and Drs. Angel Gu, Monica Torres Coronado, Janet Chung, and Ms. Elizabeth Epps for performing NSG mouse transplant and HIV challenge studies presented in Fig. 1.

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Conflict of Interest

David L. DiGiusto declares that he is a co-investigator on a grant from CIRM to develop zinc finger nucleases for modifying hematopoietic stem cells that includes Sangamo Biosciences as a corporate partner. Dr. DiGiusto is currently a paid consultant to CalImmune who is developing stem cell-based HIV entry inhibitors currently being tested in phase 1 clinical trials. In addition, Dr. DiGiusto has a patent MCM-7 construct with siRNA to HIV pending. Dr. DiGiusto declares he has no stock or stock options in either of these companies and is not compensated for the work or views presented in this article.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. Department of Stem Cell and Cell Therapeutic Operations, Stanford Hospital and Clinics, 300 Pasteur Drive, Stanford, CA, 94305, USA

    David L. DiGiusto

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Correspondence to David L. DiGiusto.

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This article is part of the Topical Collection on HIV Pathogenesis and Treatment

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DiGiusto, D.L. Stem Cell Gene Therapy for HIV: Strategies to Inhibit Viral Entry and Replication. Curr HIV/AIDS Rep 12, 79–87 (2015). https://doi.org/10.1007/s11904-014-0242-8

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