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: 6358315
• 负责人: MEI SUN
• 金额: $ 3.92万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-21 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6358315
• 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.

描述：（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方面具有巨大的潜力 研究基础神经科学。例如，HSV-1 载体表达 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 帕金森病。然而，这些向量变得复杂了 副作用，例如细胞病变效应和免疫反应，引起 主要由辅助病毒引起。因此，该实验室最近 为这些载体开发了辅助无病毒包装系统。这 系统基本上解决了之前的许多问题 载体系统，但滴度较低。因此，本次联谊会 提出了两种不同的方法来增加辅助滴度 无病毒载体系统。然后将进行额外的实验 进行使用这些增加的滴度，结合改进的 表达儿茶酚胺生物合成酶的载体，以校正 6-OHDA大鼠PD模型。

项目成果

Modest increases in the titers of helper virus-free herpes simplex virus 1 (HSV-1) vectors by packaging in a cell line with inducible expression of HSV-1 VP16 or by treatment with N,N'-hexamethylene-bis-acetamide.

通过将无辅助病毒的单纯疱疹病毒 1 (HSV-1) 载体包装到可诱导表达 HSV-1 VP16 的细胞系中或用 N,N-六亚甲基双乙酰胺处理，可适度增加无辅助病毒的单纯疱疹病毒 1 (HSV-1) 载体的滴度。

• 发表时间: 2000
• 期刊: Acta virologica.
• 作者: Sun,M;Lee,J;Yu,L;Geller,AI
• 通讯作者: Geller,AI

A tyrosine hydroxylase-neurofilament chimeric promoter enhances long-term expression in rat forebrain neurons from helper virus-free HSV-1 vectors.

酪氨酸羟化酶-神经丝嵌合启动子可增强来自无辅助病毒 HSV-1 载体的大鼠前脑神经元的长期表达。

• DOI: 10.1016/s0169-328x(00)00197-2
• 发表时间: 2000
• 期刊: Brain research. Molecular brain research
• 作者: Zhang,GR;Wang,X;Yang,T;Sun,M;Zhang,W;Wang,Y;Geller,AI
• 通讯作者: Geller,AI

Enhanced reporter gene expression in the rat brain from helper virus-free HSV-1 vectors packaged in the presence of specific mutated HSV-1 proteins that affect the virion.

在存在影响病毒粒子的特定突变 HSV-1 蛋白的情况下包装的无辅助病毒 HSV-1 载体增强了大鼠大脑中报告基因的表达。

• DOI: 10.1016/s0169-328x(01)00059-6
• 发表时间: 2001
• 期刊: Brain research. Molecular brain research
• 作者: Yang,T;Zhang,GR;Zhang,W;Sun,M;Wang,X;Geller,AI
• 通讯作者: Geller,AI