HIV-specific nucleases to reservoir cells

描述（由申请人提供）：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到的水平，但这些药物并不能治愈艾滋病毒患者，因此，如果患者停止服用药物，病毒水平会迅速反弹。这种失败的主要原因是，尽管进行了药物治疗，但潜伏或储存HIV的水平仍然很低，它们隐藏在长寿命和静止的细胞中，如中枢记忆T细胞。清除这一残留病毒库的策略可以补充目前的抗逆转录病毒疗法，并使受感染的个体最终得到治愈。在这里，我们描述了一种通过将HIV特异性核酸酶靶向递送到已被证明在潜伏HIV基因组中富集的关键细胞亚群来减少潜伏库的方法。该方法使用了基于靶向核酸酶和工程化病毒载体的新兴技术，并将使用HIV潜伏期的体内模型进行评估。通过这种方式，我们建议开发一类新的治疗方法，可以有助于管理艾滋病毒感染和治愈的目标。

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.