SOMATIC GENE THERAPY FOR TYPE 1 DIABETES MELLITUS

1 型糖尿病的体细胞基因疗法

• 批准号: 2774160
• 负责人: ROBERT C MCEVOY
• 金额: $ 4.53万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2774160
• 关键词: Retroviridae; disease /disorder model; fibroblast growth factor; ganciclovir; gene expression; gene therapy; genetic transduction; immunocytochemistry; insulin; insulin dependent diabetes mellitus; laboratory rat; liver cells; proinsulin; thymidine kinase; transfection /expression vector

In concept, the goal of this project is quite simple - to use somatic gene therapy to correct the metabolic defects resulting in the diseases known as type 1 and type 2 diabetes mellitus. These are diseases with some similarities but more differences. The amelioration of their consequences is unlikely to be as simple as transducing the liver to produce insulin. In type 1 diabetes in which insulin deficiency is the major problem, the need for insulin varies several fold during the course of the day. In type 2 diabetes, the defect is not completely understood, but therapy directed only at additional insulin replacement is unlikely to be completely successful. Dr. Woo and his colleagues have planned a series of approaches to address these complex diseases. The project in which I will be involved will add a "suicide gene", that of thymidine kinase, to the molecular construct containing the insulin gene whose expression is driven by a retroviral promotor. This will address directly an obvious problem in gene therapy for type 1 diabetes - the possibility of producing hypoglycemia from excessive expression of the trans gene. This project will provide experience in every aspect from conception to cloning of the relevant gene, packing in virus, and the therapy itself.

从概念上讲，这个项目的目标很简单--使用躯体 基因治疗纠正导致疾病的代谢缺陷 被称为1型和2型糖尿病。这些疾病都是 有一些相似之处，但更多的不同之处。他们的改进 后果不太可能像将肝脏转移到 产生胰岛素。在1型糖尿病中，胰岛素缺乏是 主要问题是，对胰岛素的需求在过去几年变化了好几倍 一天中的当然。在2型糖尿病中，这种缺陷并不完全 明白，但治疗只针对额外的胰岛素替代 不太可能完全成功。吴博士和他的同事们 已经计划了一系列方法来应对这些复杂的疾病。 我将参与的项目将增加一个“自杀基因”，即 胸苷激酶，到含有胰岛素的分子结构 由逆转录病毒启动子驱动表达的基因。这将是 直接解决1型糖尿病基因治疗中的一个明显问题 -过度表达导致低血糖的可能性 转基因的基因。这个项目将提供各方面的经验。 从受孕到相关基因的克隆，包装成病毒，以及 治疗本身。