HIV-specific nucleases to reservoir cells

描述(申请人提供)：尽管目前的抗艾滋病毒药物取得了成功，通常可以将患者体内的病毒水平降低到无法检测的水平，但这些药物并不能治愈人们的艾滋病毒，因此如果患者停止服用药物，病毒水平就会迅速反弹。这一失败的主要原因是，尽管进行了药物治疗，潜伏或储存的艾滋病毒水平仍然很低，隐藏在长期存活和静止的细胞中，如中央记忆T细胞。清除这种残留储存库的策略可以补充目前的抗逆转录病毒疗法，并允许最终治愈受感染的人。在这里，我们描述了一种方法，通过有针对性地将HIV特异性核酸酶传递到已被证明在潜伏的HIV基因组中富含的关键细胞子集，来减少潜伏的病毒储存库。该方法使用基于靶向核酸酶和工程病毒载体的新兴技术，并将使用艾滋病毒潜伏期的体内模型进行评估。通过这种方式，我们建议开发一种新的治疗方法，可以为艾滋病毒感染的管理和治愈目标做出贡献。

DESCRIPTION (provided by applicant): Despite the success of current anti-HIV drugs, which can often reduce levels of virus in a patient to undetectable levels, the drugs do not cure people of HIV, so that virus levels rapidly rebound if a patient stops taking the drugs. The major reason for this failure is that low levels of latent or reservoir HIV remain despite the drug treatment, hiding out in long-lived and quiescent cells such as central memory T cells. Strategies that removed this residual reservoir could complement current antiretroviral therapies and allow for the eventually cure of infected individuals. Here, we describe an approach to reduce the latent reservoir through the targeted delivery of HIV-specific nucleases to a key subset of cells that has been shown to be enriched in latent HIV genomes. The approach uses emerging technologies based on targeted nucleases and engineered viral vectors, and will be evaluated using in vivo models of HIV latency. In this way we propose to develop a new class of therapeutics that could contribute to the management of HIV infection and the goal of a cure.