Eliminating the latent reservoir by targeted in vivo delivery of HIV-specific CARs

项目摘要 要广泛实施艾滋病毒治疗方法，这些方法必须安全、负担得起和 非常有效。允许治疗剂被注入到 艾滋病毒携带者(PLWH)而不是体外制造的可能代表着一种 实现这一目标的重要一步。在这项申请中，调查人员融合了他们的专业知识 在信使核糖核酸脂纳米粒(mRNA-LNPs)和HIV CAR技术方面提出发展建议 针对并清除潜在储集层的可注射药剂。这样做的一个关键优势是 方法是我们可以靶向组织和细胞，如生殖道或T卵泡 CTL被排除或活性降低的细胞。在目标1中，我们将优化 这些进行体外研究的mRNA-LNPs的组成。一旦先导化合物被 一旦确定，我们将在人源化的小鼠身上测试它们的体内活性。最后，使用 ART非人灵长类动物模型，我们将测试mRNA-LNP复合体降低 病毒式蓄水池。

Project Summary For HIV cure approaches to be widely implemented, they will need to be safe, affordable and highly effective. The development strategies that allow therapeutic agents to be infused into people living with HIV (PLWH) rather than being manufactured ex vivo may represent an important step to reaching this goal. In this application, the investigators merged their expertise in mRNA lipid nanoparticles (mRNA-LNPs) and HIV CAR technology to propose to develop injectable agents that will target and remove the latent reservoir. A key advantage of this approach is that we can target tissues and cells such as the reproductive track or T follicular cells where CTLs are either excluded or have diminished activity. In Aim 1, we will optimize the composition of these mRNA-LNPs performing in vitro studies. Once lead compounds are identified, we will test these in humanized mouse for in vivo activity. Finally, using a state of the art non-human primate model we will test the ability of mRNA-LNP complexes to reduce the viral reservoir.