DEVELOPMENT AND DELIVERY OF ANTIVIRAL RNA FOR AIDS

该项目作为我们药品的抗病毒评估实验室 探索小组。实验室将区分具体的和非具体的 使用HIV-1和对照HIV-2的抗HIV-1RNA效果将进行比较 病毒蛋白表达，DNA整合，体内切割HIV RNA，以及 传染性病毒的产生。与项目1和项目4一起， 实验室将评估其抗病毒活性和稳定性 在细胞系中内源性表达抗病毒RNA，特别是核酶 用质粒或逆转录病毒载体转化。抗HIV-1作用的研究进展 逆转录病毒转导的核酶在造血细胞中的表达 探索过了。为了评估合成核酶的抗病毒效力， 实验室将对化学和酶制剂进行比较 由美国生化公司开发的材料将 项目1和项目2的相关酶动力学和生物稳定性研究 功能性抗病毒活性。 最后，为了描述抗病毒RNA的潜在局限性， 实验室将确定核酶对非靶向细胞的影响 RNA和病毒耐药在长期培养中的发生。 该项目的总体目标将是建立和评估最优 使用核酶和其他抗病毒RNA抑制HIV的方法 确定这是否可以成为治疗艾滋病的候选方法。

This project serves as the antiviral evaluation laboratory for our Drug Discovery Group. The laboratory will characterize specific and nonspecific effects of anti-HIV-1 RNA using HIV-1 and control HIV-2 and will compare viral protein expression, DNA integration, in vivo cleavage HIV RNA, and generation of infectious virus. In conjunction with Projects 1 and 4, the laboratory will evaluate the antiviral activity and stability of endogenously expressed antiviral RNA, particularly ribozymes, in cell lines transformed with plasmid or retrovirus vectors. The anti-HIV-1 effects of retrovirus-transduced ribozyme expression in hematopoietic cells will be explored. To evaluate the antiviral potency of synthetic ribozyme, the laboratory will compare both chemically and enzymatically manufactured materials developed at United States Biochemical Corporation and will correlate enzyme kinetic and biostability studies of Projects 1 and 2 with functional antiviral activity. Finally, to characterize the potential limitations of antiviral RNA, the laboratory will determine the effect of ribozyme on non-targeted cellular RNA and on the occurence of viral resistance in long term cultures. The overall goals of this project will be to establish and evaluate optimal methods of HIV inhibition using ribozyme and other antiviral RNA to determine if this can become a candidate method for the treatment of AIDS.