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首页> 外文期刊>The Journal of Infectious Diseases >Gene therapy using a simian virus 40-derived vector inhibits the development of in vivo human immunodeficiency virus type 1 infection of severe combined immunodeficiency mice implanted with human fetal thymic and liver tissue.
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Gene therapy using a simian virus 40-derived vector inhibits the development of in vivo human immunodeficiency virus type 1 infection of severe combined immunodeficiency mice implanted with human fetal thymic and liver tissue.

机译：使用猿猴病毒40衍生的载体进行基因治疗可抑制植入人胎胸腺和肝组织的严重联合免疫缺陷小鼠体内人免疫缺陷病毒1型感染的发展。

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摘要

To evaluate the in vivo efficacy of gene therapy for treating human immunodeficiency virus type 1 (HIV-1) infection, a novel simian virus (SV) 40-derived vector gene delivery system that efficiently transduces human leukocytes was combined with a model using severe combined immunodeficiency mice infected with HIV-1 and implanted with human fetal thymic and liver tissue (thy/liv-SCID-hu mice). The SV40-derived vector, SV(Aw), which encodes a variable fragment antibody recognizing HIV-1 integrase (IN#33),was injected into the human thymic grafts of thy/liv-SCID-hu mice and induced IN#33 expression in most of the thymocytes in the graft. After in vivo challenge with HIV-1, IN#33 expression inhibited in vivo HIV-1 infection, as evidenced by the markedly lower number of HIV-1-infected thymocytes detected in human thymic grafts injected with the SV(Aw) vector, compared with those injected with a control SV40-derived vector. Thus, these findings demonstrate the utility of this new mouse model system for assessing the in vivo efficacy of HIV-1-specific gene therapy. In addition, these data indicate that SV40-derived vectors may provide a system capable of efficient in vivo gene delivery.
机译：为了评估基因疗法治疗1型人类免疫缺陷病毒（HIV-1）感染的体内功效，将有效转导人白细胞的新型猿猴病毒（SV）40衍生载体基因传递系统与模型结合起来，使用严格的联合疗法感染HIV-1并植入人胎儿胸腺和肝组织的免疫缺陷小鼠（thy / liv-SCID-hu小鼠）。将SV40衍生的载体SV（Aw）编码识别HIV-1整合酶（IN＃33）的可变片段抗体，然后注入thy / liv-SCID-hu小鼠的人胸腺移植物中并诱导IN＃33表达在移植物中的大多数胸腺细胞中。在体内接受HIV-1攻击后，IN＃33表达抑制了体内HIV-1感染，这与注射SV（Aw）载体的人胸腺移植物中检测到的HIV-1感染胸腺细胞数量明显减少所证明注射了对照SV40衍生载体的药物。因此，这些发现证明了这种新的小鼠模型系统在评估HIV-1特异性基因治疗的体内功效中的实用性。另外，这些数据表明源自SV40的载体可以提供能够有效体内基因递送的系统。

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