Abstract
Immunodeficient mice reconstituted with human CD4+ T cells, which can be achieved either by transfer of mature cells or immature progenitors, represent the only animal model to study HIV-1 infection of human lymphocytes in vivo. However, the immunocompromised status of most of these models currently rule out their use for vaccine studies. Nevertheless, the model might be ideally suited for HIV-1 gene therapy studies since eliciting an efficient anti-viral immune response is not the primary end-point. Rather, HIV-1 gene therapy should protect CD4+ T cells from HIV-1- induced deletion and/or reduced viral replication. Here, we describe recent advancements in the field of HIV-1 gene therapy, focusing on tools and targets validated in various models of humanized mice. From the analysis of this literature, it appears that strategies targeting viral entry, by means of neutralizing antibodies or fusion inhibitors, are the most promising so far. Indeed, strategies targeting viral entry have moved to the clinic with encouraging results. Thus, humanized mice should be considered as the prime model to devise the safer and most effective HIV-1 gene therapy strategy.
Keywords: HIV-1, Gene therapy, Humanized mice, CCR5, CD4+ T cells, DNA, RAG.
Current Gene Therapy
Title:Lessons From HIV-1 Gene Therapy in Humanized Mice: Is Targeting Viral Entry the Road to Success?
Volume: 16 Issue: 1
Author(s): Nicolas Petit and Gilles Marodon
Affiliation:
Keywords: HIV-1, Gene therapy, Humanized mice, CCR5, CD4+ T cells, DNA, RAG.
Abstract: Immunodeficient mice reconstituted with human CD4+ T cells, which can be achieved either by transfer of mature cells or immature progenitors, represent the only animal model to study HIV-1 infection of human lymphocytes in vivo. However, the immunocompromised status of most of these models currently rule out their use for vaccine studies. Nevertheless, the model might be ideally suited for HIV-1 gene therapy studies since eliciting an efficient anti-viral immune response is not the primary end-point. Rather, HIV-1 gene therapy should protect CD4+ T cells from HIV-1- induced deletion and/or reduced viral replication. Here, we describe recent advancements in the field of HIV-1 gene therapy, focusing on tools and targets validated in various models of humanized mice. From the analysis of this literature, it appears that strategies targeting viral entry, by means of neutralizing antibodies or fusion inhibitors, are the most promising so far. Indeed, strategies targeting viral entry have moved to the clinic with encouraging results. Thus, humanized mice should be considered as the prime model to devise the safer and most effective HIV-1 gene therapy strategy.
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Petit Nicolas and Marodon Gilles, Lessons From HIV-1 Gene Therapy in Humanized Mice: Is Targeting Viral Entry the Road to Success?, Current Gene Therapy 2016; 16 (1) . https://dx.doi.org/10.2174/1566523216666160104141644
DOI https://dx.doi.org/10.2174/1566523216666160104141644 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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