Gene transfer in humans using a conditionally replicating lentiviral vector
Gene transfer in humans using a conditionally replicating lentiviral vector
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DOI：
10.1073/pnas.0608138103
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发表时间：
2006-11-14
影响因子：
11.1
通讯作者：
June, Carl H.
中科院分区：
文献类型：
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作者：
Levine, Bruce L.;Humeau, Laurent M.;June, Carl H.
我们报告了一项针对HIM的I期开放标签非随机临床试验中慢病毒载体的临床评估结果。该试验评估了一种有条件复制的HIV-1衍生载体的安全性，该载体表达一种针对HIV包膜的反义基因。5名对至少两种抗病毒治疗方案无效的慢性HIV感染者被纳入研究。单次静脉输注基因修饰的自体CD4 T细胞在所有患者中耐受性良好。病毒载量稳定，其中一名受试者表现出病毒载量持续下降。4名受试者的CD4计数保持稳定或增加，并观察到持续的基因转移。5例患者中有4例观察到载体的自限性动员。观察21-36个月后，没有插入性突变的证据。四名受试者的免疫功能有所改善。慢病毒载体似乎有希望将基因转移到人类身上。
We report findings from a clinical evaluation of lentiviral vectors in a phase I open-label nonrandomized clinical trial for HIM This trial evaluated the safety of a conditionally replicating HIV-1-derived vector expressing an antisense gene against the HIV envelope. Five subjects with chronic HIV infection who had failed to respond to at least two antiviral regimens were enrolled. A single i.v. infusion of gene-modified autologous CD4 T cells was well tolerated in all patients. Viral loads were stable, and one subject exhibited a sustained decrease in viral load. CD4 counts remained steady or increased in four subjects, and sustained gene transfer was observed. Self-limiting mobilization of the vector was observed in four of five patients. There is no evidence for insertional mutagenesis after 21-36 months of observation. immune function improved in four subjects. Lentiviral vectors appear promising for gene transfer to humans.