BIODEGRADABLE NANOPARTICLES FOR AIDS GENE THERAPY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 取代“坏的”DNA或用治疗性DNA治疗患者是治疗遗传性和感染性疾病的一种很有前途的方法。人类免疫缺陷病毒(HIV)诱导的艾滋病发生在旨在保护我们的身体免受疾病侵袭的细胞中，我们的免疫细胞。我们实验室的目标是专门针对这些细胞进行基因治疗，以减少艾滋病毒的复制，减缓艾滋病的进展。目前的艾滋病毒治疗依赖于高剂量的药物来抑制免疫细胞，作为阻断艾滋病毒复制位点的一种手段；然而，这些药物损害了患者的免疫系统。以减少特定参与艾滋病毒复制的免疫细胞的遗传物质为目标是可取的。基于病毒或脂质体(小脂膜)的基因传递载体具有吸引力，因为它们能够靶向细胞并感染治疗性DNA，但通常会引发免疫反应，而且往往是有毒的。我们的目标是开发DNA输送载体，通过使用FDA批准的材料，如聚(DL-乳酸-羟基乙酸)或小肽，安全有效地将DNA输送到免疫细胞。归根结底，这些安全材料必须具有便于将DNA输送到免疫细胞的特性。最初的研究重点是筛选具有免疫细胞(巨噬细胞和T细胞)的DNA递送载体的不同配方，以确定DNA递送的最佳配方。然后，将在模拟艾滋病毒诱导的艾滋病的小鼠身上对选定的配方进行评估。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Replacing "bad" DNA or treating patients with therapeutic DNA represents a promising approach to treating inherited as well as infectious diseases. Human Immunodeficiency Virus (HIV)-induced AIDS occurs in the cells designed to protect our bodies from disease, our immune cells. Our lab aims to direct gene therapy specifically to these cells to reduce HIV replication and slow the progress to AIDS. Current HIV therapy relies on high doses of drugs that suppress immune cells as a means to block the replication sites of HIV; however, these drugs compromise the patient's immune system. Targeting genetic material that would reduce immune cells specifically involved in HIV replication is desired. Gene delivery vehicles based on viruses or liposomes (small lipid envelopes) are attractive in terms of their ability to target and infect cells with therapeutic DNA, but typically initiate an immune response and are often toxic. Our goal is to develop DNA delivery vehicles that safely and effectively deliver DNA to immune cells by using FDA approved materials such as poly(DL-lactic-co-glycolic acid) or small peptides. Ultimately, these safe materials must be endowed with properties that facilitate the delivery of DNA to immune cells. Initial studies focus on screening different formulations of DNA delivery vehicles with immune cells (macrophages and T-cells) to determine optimal formulations for DNA delivery. Selected formulations will then be evaluated in mice modeling HIV-induced AIDS.