BIODEGRADABLE NANOPARTICLES FOR AIDS GENE THERAPY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 替换“坏”DNA或用治疗性DNA治疗患者代表了治疗遗传性疾病和感染性疾病的一种有希望的方法。人类免疫缺陷病毒（HIV）诱导的艾滋病发生在旨在保护我们身体免受疾病侵害的细胞中，即我们的免疫细胞。我们实验室的目标是专门针对这些细胞进行基因治疗，以减少艾滋病毒复制并减缓艾滋病的进展。目前的HIV治疗依赖于高剂量的抑制免疫细胞的药物作为阻断HIV复制位点的手段;然而，这些药物损害了患者的免疫系统。期望靶向遗传物质，其将减少特异性参与HIV复制的免疫细胞。基于病毒或脂质体（小脂质包膜）的基因递送载体在它们用治疗性DNA靶向和感染细胞的能力方面是有吸引力的，但通常引发免疫应答并且通常是有毒的。我们的目标是开发DNA递送载体，通过使用FDA批准的聚合物如聚（DL-乳酸-乙醇酸共聚物）安全有效地将DNA递送到免疫细胞。最终，这些安全的材料必须具有促进将DNA递送到免疫细胞的特性。最初的研究集中在筛选具有免疫细胞（巨噬细胞和T细胞）的DNA递送载体的不同制剂，以确定用于DNA递送的最佳制剂。然后在HIV诱导的AIDS小鼠模型中评价所选制剂。

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 polymers such as poly(DL-lactic-co-glycolic acid). 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.