Falkenhagen Alexander, Joshi Sadhna
Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada.
Mol Ther Nucleic Acids. 2018 Dec 7;13:514-533. doi: 10.1016/j.omtn.2018.09.018. Epub 2018 Sep 29.
Conventional HIV gene therapy approaches are based on engineering HIV target cells that are non-permissive to viral replication. However, expansion of gene-modified HIV target cells has been limited in patients. Alternative genetic strategies focus on generating gene-modified producer cells that secrete antiviral proteins (AVPs). The secreted AVPs interfere with HIV entry, and, therefore, they extend the protection against infection to unmodified HIV target cells. Since any cell type can potentially secrete AVPs, hematopoietic and non-hematopoietic cell lineages can function as producer cells. Secretion of AVPs from non-hematopoietic cells opens the possibility of using a genetic approach for HIV prevention. Another strategy aims at modifying cytotoxic T cells to selectively target and eliminate infected cells. This review provides an overview of the different genetic approaches for HIV treatment and prevention.
传统的HIV基因治疗方法是基于对不允许病毒复制的HIV靶细胞进行改造。然而，基因修饰的HIV靶细胞在患者体内的扩增一直受到限制。替代基因策略则侧重于生成分泌抗病毒蛋白（AVP）的基因修饰的生产细胞。分泌的AVP会干扰HIV的进入，因此，它们将对感染的保护扩展到未修饰的HIV靶细胞。由于任何细胞类型都有可能分泌AVP，造血和非造血细胞谱系都可以作为生产细胞。非造血细胞分泌AVP为采用基因方法预防HIV开辟了可能性。另一种策略旨在改造细胞毒性T细胞，以选择性地靶向和消除受感染细胞。本综述概述了用于HIV治疗和预防的不同基因方法。
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