CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape.
CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape.
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DOI：
10.3390/v7082816
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发表时间：
2015-07-27
期刊：
影响因子：
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通讯作者：
Symonds G
中科院分区：
文献类型：
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作者：
Hütter G;Bodor J;Ledger S;Boyd M;Millington M;Tsie M;Symonds G
2008年，在一名HIV感染者体内进行了CCR 5-delta 32（CCR 5-d32）纯合子干细胞的异基因移植，导致了持续的病毒控制，并可能根除了HIV。自那时以来，人们对将这一方法推广到更广泛的人群表现出高度的兴趣。有两种细胞方式可以做到这一点。第一种是使用CCR 5阴性细胞来源，例如，造血干细胞（HSC）复制最初的发现。然而，最近一例使用CCR 5-d32纯合干细胞进行的第二次同种异体移植发生了CXCR 4准种的病毒逃逸。第二种方法是通过基因治疗来敲低CCR 5的表达。目前，有五种有前途的技术，其中三种目前正在临床测试。这些技术包括锌指核酸酶（ZFN）、成簇规则间隔回文重复序列/CRISPR相关蛋白9核酸酶（CRISPR/Cas9）、转录激活因子样效应物核酸酶（TALEN）、短发夹RNA（shRNA）和核酶。虽然有多种基因治疗策略正在测试中，在这篇综述中，我们反映了我们目前的知识抑制CCR 5具体和这种方法是否允许随之而来的病毒逃逸。
Allogeneic transplantation with CCR5-delta 32 (CCR5-d32) homozygous stem cells in an HIV infected individual in 2008, led to a sustained virus control and probably eradication of HIV. Since then there has been a high degree of interest to translate this approach to a wider population. There are two cellular ways to do this. The first one is to use a CCR5 negative cell source e.g., hematopoietic stem cells (HSC) to copy the initial finding. However, a recent case of a second allogeneic transplantation with CCR5-d32 homozygous stem cells suffered from viral escape of CXCR4 quasi-species. The second way is to knock down CCR5 expression by gene therapy. Currently, there are five promising techniques, three of which are presently being tested clinically. These techniques include zinc finger nucleases (ZFN), clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 nuclease (CRISPR/Cas9), transcription activator-like effectors nuclease (TALEN), short hairpin RNA (shRNA), and a ribozyme. While there are multiple gene therapy strategies being tested, in this review we reflect on our current knowledge of inhibition of CCR5 specifically and whether this approach allows for consequent viral escape.