Nonhuman Primate Core

核心C：项目总结/摘要 造血干细胞和祖细胞（HSPCs）移植是唯一已知的HIV-1病例的基础 功能性治疗然而，在这项开创性的临床病例研究之后的12年里， 为了将该案例研究应用于更广泛的HIV+个体，需要进行以下研究：我们的首要目标是 U19联盟将确定候选策略，以安全有效地修饰患者自身的HSPC， 艾滋病毒感染，并同时增强其识别和破坏感染细胞的能力。非人 灵长类动物（NHP）核心将在组织临床前方面发挥核心作用， 我们小组的一个项目，保持对最适合未来试验的预防性相关功能的关注 在病人身上。在项目1（厨房）中，我们将产生一系列12个NHP， 基因修饰的HSPC。这些细胞将表达一种有希望的病毒特异性免疫效应分子，称为 CD 4CAR，与其他有前景的疗法如广泛中和抗体（bNAb）组合，以及 治疗性疫苗CD 4CAR修饰的HSPC子代，与bNAb和疫苗特异性抗体组合 细胞，代表了一个强大的和协同的方法，以目标病毒的持久性。在项目2（Morizono）中， 将专注于基因修饰HSPC的方法，而不将它们从体内取出，共研究了9种 NHP。所谓的“体内递送”方法将显著提高抗HIV基因的适用性， 为世界各地的患者提供治疗。在项目3（An）中，我们将在总共6个NHP中测试另一个重要方面： 精确调节基因修饰的HSPC及其后代离体和体内水平的能力。每个 NHP核心项目的特定功能将在密切磋商的情况下，着眼于诊所进行评估 与我们在Project 4（Symonds）中的长期合作伙伴合作。NHP核心提出的目标是实现 上述每项NHP研究都使用有效的慢病毒生产基因修饰的NHP HSPC产品 载体，并为每个项目中的动物提供支持性护理，无论是在HSPC基因治疗后， 感染艾滋病毒样病毒。我们联合体的四个项目都具有很强的互补性。我们将 连接每个项目监督的大型动物研究，为有关协同作用的讨论做出有意义的贡献 在项目之间，并评估新的和有前途的疗法，因为他们出现。

Core C: Project Summary/Abstract Transplantation of hematopoietic stem and progenitor cells (HSPCs) underlies the only known case of HIV-1 functional cure. Over 12 years after this pioneering clinical case study, however, substantial improvements are needed in order to apply this case study to a broader spectrum of HIV+ individuals. The overarching goal of our U19 consortium is to identify candidate strategies to safely and effectively modify a patient's own HSPCs to resist HIV infection, and simultaneously enhance their ability to recognize and destroy infected cells. The Nonhuman Primate (NHP) Core will play a central role in organizing preclinical aspects of the approaches proposed by each project in our group, maintaining a focus on translationally relevant features that are best suited for future trials in patients. In Project 1 (Kitchen), we will generate a series of 12 NHPs that are transplanted with autologous, gene-modified HSPCs. These cells will express a promising virus-specific immune effector molecule known as CD4CAR, in combination with other promising therapies such as broadly neutralizing antibodies (bNAbs), and therapeutic vaccination. CD4CAR-modified HSPC progeny, in combination with bNAbs and vaccine-specific cells, represent a formidable and synergistic approach to target virus persistence. In Project 2 (Morizono), we will focus on approaches to gene-modify HSPCs without removing them from the body, studying a total of 9 NHP. So-called “in vivo delivery” approaches will significantly enhance the applicability of anti-HIV gene therapies to patients around the world. In Project 3 (An), we will test another important aspect in a total of 6 NHP: the ability to precisely regulate the levels of gene-modified HSPCs and their progeny ex vivo and in vivo. Each of the NHP Core's project-specific functions will be assessed with an eye towards the clinic, in close consultation with our longstanding partners in Project 4 (Symonds). The goals set forth by the NHP Core are to implement each of the NHP studies described above, produce gene-modified NHP HSPC products using potent lentiviral vectors, and to provide supportive care for animals in each project, both following HSPC gene therapy and infection with HIV-like viruses. Each of the four projects in our consortium are highly complementary. We will bridge large animal studies overseen by each project, contribute meaningfully to discussions regarding synergies between projects, and evaluate new and promising therapies as they emerge.