CORE--IMMUNOLOGY/PATHOLOGY FACILITY

核心--免疫学/病理学设施

• 批准号: 6369124
• 负责人: MARK A. ATKINSON
• 金额: $ 18.75万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-25 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6369124
• 关键词: adeno associated virus group; biomedical facility; cellular pathology; gene therapy; metabolism disorder; microorganism immunology; tissue /cell culture

The Immunology/Pathology of The University of Florida Gene Therapy enter has been formed to assist investigators participating in gene therapy projects aimed at reversing and/or preventing phenyhlketonuria (PKU), alpha-1-anti-trypsin (AAT) deficiency, disorders of glycogen storage, and pilot projects related to diseases of the liver. Specifically, the Core will support these investigations by performing immunological and pathological analyses that characterize the host's immune system and cell/tissue response to agents proposed for or actively used in clinical trials based on gene therapy. This goal will be accomplished by performance of two specific aims: 1) Determine the immunogenicity of recombinant adeno-associated virus (rAAV) transgene products and capsid protein administered to animals in studies investigating long-term therapeutic gene transfer and expression; 2) Determine the tissue compartment of engraftment in host tissue, both with respect to site(s) of engraftment and toxicity of endogenous host tissues. Such studies Are vital in order to evaluate whether engraftment and toxicity to endogenous host tissues. Such studies are vital in order to evaluate whether methods for limiting/eliminating immune responses against vector capsid proteins and transgene products or directing engraftment/reducing cellular toxicity (were they identified) require development. Specific examples of vector based systems to which these services will be provided/applied include the rAAV, rAAV-green fluorescent protein, rAAV-acid alpha- glucosidase, and adenovirus infection based systems. In addition to providing a critical element for assurance of therapeutic safety, the Immunology/Pathology Core should provide information that will enhance the feasibility and efficacy of gene delivery trials.

佛罗里达大学的免疫学/病理学基因治疗中心已经成立，以协助参与基因治疗项目的研究人员，这些项目旨在逆转和/或预防苯丙酮尿症(PKU)、α-1抗胰酶(AAT)缺乏症、糖原储存障碍以及与肝脏疾病相关的试点项目。具体地说，核心将通过执行免疫学和病理学分析来支持这些研究，这些分析描述了宿主的免疫系统和细胞/组织对建议用于或积极用于基于基因治疗的临床试验的药物的反应。这一目标将通过两个特定目标的实现来实现：1)在研究长期治疗性基因转移和表达的研究中，确定重组腺相关病毒转基因产品和衣壳蛋白用于动物的免疫原性；2)确定移植到宿主组织中的组织分区，包括植入部位(S)和内源性宿主组织的毒性。这些研究对于评估植入性和对内源性宿主组织的毒性是至关重要的。这些研究对于评估限制/消除针对载体衣壳蛋白和转基因产物的免疫反应或指导植入/降低细胞毒性的方法(已确定)是否需要开发至关重要。将提供/应用这些服务的基于载体的系统的具体例子包括rAAV、rAAV-绿色荧光蛋白、rAAV-酸性α-葡萄糖苷酶和基于腺病毒感染的系统。除了为保证治疗安全性提供关键因素外，免疫学/病理学核心还应提供信息，以加强基因传递试验的可行性和有效性。