CRISPR/Cas9 technology toward understanding HIV latency in primary cells

接受高效联合抗逆转录病毒治疗的患者中存在潜伏的艾滋病毒 (购物车)已经很好地建立了。如果没有额外的治疗，个人必须无限期地接受ART 以避免发展为严重的免疫缺陷和病毒的传播。因为它的存在 这种蓄水池、治疗中断总是会导致病毒反弹。因此，人们普遍认为 要根除这种病毒，就需要消除潜伏的宿主。 这项建议基本目标是使我们的主要基于中医药的检测方法用于HIV-1潜伏期 可通过CRISPR/CAS9技术测试潜伏期调节基因。我们的 因此，最初的靶点将是被广泛接受的候选基因，这些基因对 建立/维护延迟或从延迟中重新激活，以及一些以前未测试过的 在不同的实验室通过基因筛查确定的基因。 成功验证控制病毒潜伏的新基因/蛋白将导致识别 相关的途径和机制研究，有可能产生重大的新倡议 开发新的治疗方法。

The presence of latent HIV in individuals treated with highly active combination antiretroviral therapy (cART) has been well established. Without additional therapies, individuals must remain on ART indefinitely in order to avoid development of severe immunodeficiency and spread of the virus. Because of the existence of this reservoir, treatment interruption invariably leads to viral rebound. Thus, it is generally accepted that eradication of the virus will require elimination of the latent reservoir. The fundamental goal of this proposal is adapt our primary TCM-based assay for HIV-1 latency described above to be amenable for testing of latency regulator genes via CRISPR/Cas9 technology. Our initial targets will therefore be candidate genes that are widely accepted to be important for either the establishment/maintenance of latency or for reactivation from latency, and a number of previously untested genes that were identified through genetic screens in various laboratories. Successful validation of novel genes/proteins that control viral latency will lead to identification of relevant pathways and mechanistic studies that will have the potential to spawn major new initiatives to develop novel therapeutics.