IMPROVED HELPER VIRUS FREE HSV VECTORS AND PARKINSONS

改进的无 HSV 载体和帕金森病辅助病毒

• 批准号: 6078208
• 负责人: MEI SUN
• 金额: $ 3.67万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-21 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6078208
• 关键词: 6 hydroxydopamine; Parkinson's disease; cell line; disease /disorder model; gene therapy; helper virus; herpes simplex virus 1; laboratory rat; neurotrophic factors; recombinant virus; transfection /expression vector

DESCRIPTON: (Applicant's abstract) Herpes Simplex Virus (HSV-1) vector have great potential for gene therapy of neurological diseases and for studies in basic neuroscience. For example, HSV-1 vectors that express tyrosine hydroxylase have supported long-term (1 year) biochemical and behavioral correction of the 6-hydorxydopamine (6-OHDA) rat model of Parkinson's disease. However, these vectors have been complicated by side effects, such as cytopathic effects and immune responses, caused principally by the helper virus. Therefore, this laboratory recently developed a helper virus-free packaging system for these vectors. This system substantially addresses many of the previous problems with the vector system, but suffer from low titers. Therefore, this fellowship proposes two different approaches to increase the titers of the helper virus-free vector system. And then additional experiments will be performed to use these increased titers, in combination with improved vectors for expressing catecholamine biosynthetic enzymes, to correct the 6-OHDA rat model of PD.

HSPOTON：（申请人摘要）单纯疱疹病毒（HSV-1）载体 在神经系统疾病的基因治疗和 基础神经科学研究。例如，表达HSV-1的载体 酪氨酸羟化酶支持长期（1年）生化和 6-羟多巴胺（6-OHDA）大鼠模型的行为矫正 帕金森氏症。然而，这些载体已经被复杂化， 副作用，如细胞病变效应和免疫反应，引起 主要是辅助病毒。因此，该实验室最近 为这些载体开发了无辅助病毒的包装系统。这 系统基本上解决了许多以前的问题， 载体系统，但遭受低滴度。因此，这个奖学金 提出了两种不同的方法来增加辅助细胞的滴度 无病毒载体系统。接下来的实验 使用这些增加的滴度，结合改善的 用于表达儿茶酚胺生物合成酶的载体， 6-OHDA大鼠PD模型。