PROPHYLAXIS OF FETAL HEMATOPOIETIC CELLS FOR FIV

描述：人类免疫缺陷病毒(HIV)具有非同寻常的 生存优势，混淆了现有的治疗方法。用短短的一代人 时间，可变的抗原性，以及大量的感染性病毒粒子，它是 毫不奇怪，尽管抗病毒药物的发展 化合物，我们只设法推迟了致命获得性疾病的发生 免疫缺陷综合征(艾滋病)。新的抗病毒疗法，特别是 插入赋予淋巴造血细胞长寿的基因 针对慢病毒感染的保护提供了一种新的方法 抗击艾滋病毒感染。到目前为止，这种疗法的效用是 受阻于可用于治疗的造血干细胞数量较少 转染法。我们准备通过使用一种 丰富的胎儿造血细胞(FHC)几乎无限来源 在免疫幼稚的干细胞中。通过增加细胞目标数量 对于转基因和移植，我们将能够更快地 确定干细胞基因疗法治疗慢病毒的疗效 感染。我们将使用的动物模型系统是猫 猫体内的免疫缺陷病毒(FIV)。FIV是一种自然产生的 家猫的逆转录病毒，为 了解发病机制和开发有效的治疗方法 与艾滋病毒直接相关的抗病毒治疗和疫苗。海流 建议开发基于核酶的抗FIV基因疗法 靶向调控基因rev及其同源基因在猫中的感染 识别序列，转速响应元件(RRE)，这对 病毒复制。针对REV和RRE的抗病毒序列将是 通过FHC使用逆转录病毒载体将其传递到猫体内。从长远来看 本研究的目的是利用这种HIV感染的动物模型来 确定是否可以通过清髓减少逆转录病毒负担 终生的血细胞来源，受到预防性保护 对抗逆转录病毒感染，可能为个人提供一种新的治疗方法 感染了艾滋病毒。

DESCRIPTION: Human immunodeficiency virus (HIV) has an extraordinary survival advantage, confounding existing therapies. With a short generation time, variable antigenicity, and a large number of infective virions, it is hardly surprising that despite the development of anti-viral pharmaceutical compounds, we have managed to only delay the onset of the fatal acquired immunodeficiency syndrome (AIDS). Novel antiviral therapy, specifically the insertion of genes which endow lymphohematopoietic cells with life-long protection against lentivirus infections offers a fresh approach to combating HIV infection. To date, the utility of this therapy has been hampered by the small number of hematopoietic stem cells available for transfection. We are poised to overcome these impediments by using a virtually limitless source of fetal hematopoietic cells (FHC) which are rich in immunologically-naive stem cells. By increasing the cell target numbers for transfection and transplantation we will be able to more rapidly determine the efficacy of stem cell gene therapy for treatment lentivirus infection. The animal model system we will employ is the feline immunodeficiency virus (FIV) in cats. FIV is a naturally-occurring retrovirus of domestic cats that provides valuable resources for understanding mechanisms of pathogenesis and for development of effective antiviral therapy and vaccines with direct relevance to HIV. The current proposal is to develop ribozyme based antiviral gene therapy against FIV infection in cats by targeting the regulatory gene rev and its cognate recognition sequences, rev response element (RRE), which are critical for virus replication. Antiviral sequences against rev and RRE will be delivered into cats using retroviral vectors by way of FHC. The long term goal of this research is to use this animal-model of HIV infection to determine whether decreasing retrovirus burden by myeloablation of a life-long source of blood cells, which are prophylactically protected against retrovirus infection, might provide a new therapy for individuals infected with HIV.