Foamy Virus Vector for Immunodeficiency Viruses Therapy

描述（由申请人提供）：随着多种组合药物治疗的出现，在延长艾滋病患者的生命方面取得了重大进展。然而，潜伏感染的存在下，休息的CD 4细胞携带复制能力的艾滋病毒已被证明在慢性感染的个人谁是抗逆转录病毒的初治以及在那些谁正在接受高效抗逆转录病毒治疗（HAART）。未能靶向潜伏感染的静息细胞是药物治疗的主要障碍。对抗HIV感染的一种不断发展的疗法是基因疗法，其涉及引入抗HIV基因以抑制病毒基因表达，从而限制HIV复制。已经建立了许多不同的抗HIV基因治疗方法来抑制病毒复制，并且该策略已经推进到HIV感染的开发治疗的最前沿。尽管这些研究令人鼓舞，但开发安全有效的载体来递送抗病毒基因仍然是一个挑战。目前用于HIV基因治疗的临床试验中的载体是低效的，因为它们不能在非分裂细胞中繁殖，或者它们的基因组不能有效地整合到宿主DNA中。基于慢病毒如HIV的载体是有希望的，因为它们可以感染分裂和非分裂细胞。尽管慢病毒在人类基因治疗中的可行性仍在使用动物模型进行探索，但慢病毒载体存在引起人类疾病的潜在风险。基于动物慢病毒的载体已经被认为是人类基因治疗中HIV载体的替代品。然而，最近报道FIV可以感染具有临床症状的非人灵长类动物，这表明使用基于动物慢病毒的载体进行人基因治疗存在风险。此外，即使慢病毒载体可以在非分裂细胞中实现有效和持续的转导和表达，它们也不能有效地使静止的CD 4细胞增殖，其中HAART治疗失败。泡沫病毒具有使其成为理想载体系统的几个固有特征。目前的建议是一个新的泡沫病毒载体的发展，有效的抗病毒治疗对猴免疫缺陷病毒（SIV）在严重联合免疫缺陷（SCID）小鼠的延续。这项提议的研究将有助于设计SFV-1载体介导的基因治疗方案，以对抗猴的SIV感染，并最终用于人类的HIV感染。

DESCRIPTION (provided by applicant): Significant progress has been made with the advent of multiple-combination drug therapy to prolong the lives of AIDS patients. However, the presence of latently infected, resting CD4 cells carrying replication-competent HIV has been demonstrated in chronically infected individuals who are antiretroviral naive as well as in those who are receiving highly active antiretroviral therapy (HAART). The failure to target the latently infected resting cells is a major impediment in drug therapy. One evolving therapy to combat HIV infection is gene therapy, which involves the introduction of anti-HIV genes to inhibit viral gene expression thereby limiting the HIV replication. Many different anti-HIV gene therapy approaches have been established to inhibit virus replication and the strategy has propelled to the forefront of developmental therapies for HIV infection. Although these studies are encouraging, development of a safe and efficient vector to deliver the antiviral genes still remains a challenge. The current vectors utilized in clinical trials for HIV gene therapy are inefficient as they cannot be propagated in non-dividing cells or their genome does not efficiently integrate into host DNA. Vectors based on lentiviruses such as HIV are promising since they can infect both dividing and non-dividing cells. Although the feasibility of lentiviruses in human gene therapy is still being explored using animal models, lentivirus vectors suffer from the potential risk of causing disease in humans. Vectors based on animal lentiviruses have been implicated as an alternative to HIV vectors for human gene therapy. However, the recent report that FIV can infect non-human primates with clinical signs indicates the risk associated with the usage of animal lentivirus based vectors for human gene therapy. Furthermore, even though lentivirus vectors can achieve effective and sustained transduction and expression in non-dividing cells they cannot efficiently transduce resting CD4 cells, where HAART therapy failed. Foamy viruses have several inherent features that make them an ideal vector system. The current proposal is a continuation in the development of novel foamy virus vectors for effective antiviral therapy against simian immunodeficiency virus (SIV) in severe combined immunodeficiency (SCID) mice. Studies from this proposal will help devise protocols for SFV-1 vector mediated gene therapy against SIV infection in monkeys and eventually for HIV infection in humans.