GROWTH FACTOR ENHANCED RETROVIRAL GENE TRANSFER TO CNS

生长因子增强逆转录病毒基因向中枢神经系统的转移

• 批准号: 6625484
• 负责人: RAYMOND J COLELLO
• 金额: $ 18.13万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-15 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6625484
• 关键词: Parkinson's disease; beta galactosidase; biotechnology; brain cell; cell proliferation; cell type; central nervous system; drug administration rate /duration; epidermal growth factor; fibroblast growth factor; gene therapy; growth factor; immunocytochemistry; laboratory rat; morphometry; murine leukemia virus; nervous system regeneration; neural degeneration; neurologic manifestations; nonhuman therapy evaluation; platelet derived growth factor; serial analysis of gene expression; technology /technique development; transfection /expression vector; tyrosine 3 monooxygenase

DESCRIPTION: (Adapted from the Applicant's Abstract) While retroviral vectors could potentially be incorporated as a tool for delivering genetic material into the CNS, the use of these vectors has been limited in the brain and spinal cord because of the lack of robust cell division. The applicant speculated that this inherent limitation of MLV based viral vectors could potentially be overcome by utilizing the known mitogenic effect of several different growth factors on cells of the CNS. Different growth factors effect cell division in different cell types. Using this information the PI has hypothesized that an in vivo application of growth factor could enhance MLV based gene transfer to the adult brain. The goal of the present application is to examine further this technical approach of gene transfer to the brain, a region with poor numbers of dividing cells even after injury or during disease states. In aim one, the applicant proposes to determine the dose response curves for growth factor (eg., FGF,PDGF, EGF) induced mitogenesis. These studies will help establish the concentration of growth factor required to optimize cell division in vivo. Aim 2 will identify and quantify the particular cell types transduced in animals first primed with a specific growth factor and subsequently given an injection of MLV based vectors expressing a marker gene. These experiments will allow the applicant to determine if the administration of a growth factor enables one to target specific cell types for gene delivery to the CNS. In aim 3, animals treated with growth factor and MLV vectors will be allowed to survive for up to 6 months. The cell types transduced in these animals will be determined and quantified so as to allow the assessment of longevity of the transgene for each of the cell populations that can be targeted. Aim 4 will test the therapeutic potential of the gene transfer approach in the rat model of Parkinson's disease. In this model the biochemical and behavioral changes associated with this treatment will be analyzed. It is hoped that these proposed experiments will lead to a new generation of studies designed to broaden the application of MLV vectors to include other neurodegenerative disease models of the CNS.

描述：（改编自申请人摘要）逆转录病毒载体

项目成果

Epidermal growth factor-induced cell proliferation in the adult rat striatum.

表皮生长因子诱导成年大鼠纹状体细胞增殖。

• DOI: 10.1016/j.brainres.2003.12.054
• 发表时间: 2004
• 期刊: Brain research.
• 作者: McGinn,MelissaJ;Sun,Dong;Schneider,StacieL;Alexander,JohnK;Colello,RaymondJ
• 通讯作者: Colello,RaymondJ