Development of tools to modify globin gene expression in stem cells

描述（由申请人提供）：开发修饰干细胞中珠蛋白基因表达的工具。本提案的目的是开发镰状细胞病患者的治疗方法。开发治疗镰状细胞病等常见遗传疾病的方法仍然是一个难以实现的目标。基因疗法是一种有潜力克服镰状细胞病治疗发展中几个问题的技术。血红蛋白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。它们易于获取，在实验室中操作，并且可以返回给患者。本课题旨在构建优化的基因表达载体，降低突变型镰状β -珠蛋白水平，同时增加另一种正常珠蛋白基因的表达，从而维持血红蛋白表达的平衡，这对正常红细胞的形成至关重要。这些载体将在人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。

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.