HIV-1 INHIBITION BY DELIVERY OF 2'5'OAS AND PKR GENES

描述：(改编自申请者摘要)这是第一份申请 竞争续集的修订版。在这份修订的提案中， 研究人员希望寻求一种基因疗法来治疗艾滋病毒 重点是增强已发现的天然抗病毒防御途径 在牢房里。他们已经表达了2个由HIV LTR控制的基因 靶细胞，并表明这些细胞受到保护，不受感染 爱滋病毒。这些基因(2‘，5’-寡腺苷合成酶和p68激酶)是 通常由干扰素诱导，是细胞抗病毒的一部分 防御机制。在以下情况下，此策略具有许多潜在的优势 与其他基因治疗策略相比：1)因为基因产物是 它们不应诱导宿主免疫系统：2)因为 由于在未感染的细胞中缺乏dsRNA，它们应该不会对非感染细胞产生毒性。 被感染的细胞；以及3)由于这些基因是人类起源的，病毒应该 不能对这一策略产生抵触情绪。HIV-1的抑制作用 在转导分化的菌株中复制(M嗜性和T嗜性菌株) 将对细胞群体进行检查。描述了一些研究以确定 这些结构对潜伏感染细胞中HIV重新激活的影响。 这一策略与传统疗法的结合将得到检验。

DESCRIPTION: (Adapted from Applicant's Abstract) This application is the first revision of a competing continuation. In this revised proposal the investigators wish to pursue a gene therapy approach to the treatment of HIV that focuses on the enhancement of the natural antiviral defense pathways found in cells. They have expressed 2 genes that are controlled by the HIV LTR in target cells and have shown that these cells are protected from infection with HIV. These genes (2',5'-oligoadenylate synthetase and the p68 kinase) are normally induced by interferon and are a part of the cellular anti-viral defense mechanisms. This strategy has a number of potential advantages when compared with other gene therapy strategies: 1) because the gene products are of human origin they should not induce the host immune system: 2) because the of the lack of dsRNA in uninfected cells they should not induce toxicity in non infected cells; and 3) since these genes are of human origin the virus should not be able to develop resistance to this strategy. The inhibition of HIV-1 replication (both M-tropic and T-tropic strains) in transduced differentiated cell populations will be examined. Studies are described to determine the effects of these constructs on HIV reactivation in latently-infected cells. Combination of this strategy with conventional therapy will be examined.