Development of tools to modify globin gene expression in stem cells

描述(由申请人提供)：开发工具来改变干细胞中珠蛋白基因的表达这项建议的目标是开发一种治疗镰状细胞疾病的方法。开发治疗常见遗传病的方法，如镰状细胞病，仍然是一个难以实现的目标。基因疗法是一项有潜力克服镰状细胞病疗法发展中的几个问题的技术。血红蛋白疾病为研究人员提供了一个主要优势，因为他们的干细胞驻留在骨髓中。它们很容易拿到，在实验室里操作，并可以回馈给患者。这项建议旨在创建优化的基因表达载体，降低突变的镰刀β-珠蛋白水平，同时增加另一个正常珠蛋白基因的表达，从而维持对正常红细胞形成至关重要的血红蛋白蛋白表达的平衡。这些载体将在人类骨髓干细胞中进行测试，以确定它们改善血红蛋白表达的潜力。 与公共卫生相关：镰状细胞病患者会出现一系列症状，包括痛苦的镰刀危机，肺、肾、肝、脾等器官的损伤，以及中风，这些都会使患者的预期寿命缩短到40岁左右，S。目前，这种常见的遗传病的大多数患者还没有根治的方法。尽管目前有许多可能的治疗方法正在研究中，这些方法可能会减少疾病的并发症或提供治愈的可能性，但这项提议寻求开发一种新的治疗方法，该方法已在其他遗传疾病的模型中显示出潜力。

DESCRIPTION (provided by applicant): Development of tools to modify globin gene expression in stem cells The objective of this proposal is to develop a treatment for patients with sickle cell disease. The development of methods for treating common genetic diseases, such as sickle cell disease remains an elusive goal. Gene therapy is a technology which has the potential to overcome several of the problems in the development of a therapy for sickle cell disease. Hemoglobinopathies offer a major advantage for researchers in that their stem cells reside in the bone marrow. They are easy to access, manipulate in the laboratory and can be given back to the patient. This proposal intends to create optimized gene expression vectors that reduce mutant sickle beta-globin protein levels while increasing the expression of another normal globin gene, thus maintaining the balance of hemoglobin protein expression that is critical to the formation of normal red blood cells. These vectors will be tested in human bone marrow stem cells to determine their potential to improve hemoglobin expression. PUBLIC HEALTH RELEVANCE: Patients with Sickle Cell Disease suffer from a range of many symptoms including painful sickle crises, damage to organs such as the lungs, kidneys, liver and spleen and stroke, which shorten life expectancy to the mid-40's. At present there is no curative treatment for majority of patients with this common genetic disease. Although there are a number of possible treatments currently under investigation which may reduce the disease complications or offer the potential of a cure, this proposal seeks to develop a new therapeutic approach that has demonstrated potential in models of other genetic diseases.