Evaluation and comparison of lentiviral and AAV vector mediated gene therapy for the mucopolysaccharidoses

慢病毒和AAV载体介导的粘多糖症基因治疗的评价和比较

• 批准号: nhmrc : 399343
• 负责人: A/Pr Donald Anson
• 金额: $ 34.76万
• 依托单位: The University of Adelaide
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/evaluation-comparison-lentiviral-therapy-mucopolysaccharidoses/82523
• 关键词: Evaluation; comparison; lentiviral; AAV; vector

The mucopolysaccharidoses are a group of inherited diseases that have profound consequences for affected individuals. They have pleiotropic effects and usually result in premature death. Although intravenous enzyme replacement therapy has been developed for a number of these disorders, this approach to therapy is invasive, very expensive, of limited efficacy, and is completely ineffective in treating brain pathology. The principal reason for this is the protected nature of the brain which prevents enzymes that are administered intravenously from entering. Therefore, alternative therapies must be considered in order to provide more effective therapy for the mucopolysaccharidoses, especially those that have significant brain pathology. Gene therapy is one such alternative therapy but this still faces the problem of introducing the therapeutic agent (in this case the gene encoding the requisite enzyme) into the brain. This project aims to provide a comparitive evaluation of two gene therapy vectors for their efficacy in treating all aspects of the pathology found in the mucopolysaccharidoses. Both vectors have the properties of being able to efficiently deliver genes to different cell types and result in the stable genetic modification of the target cell, making them ideal for long-term treatment. However, for effective gene therapy, significant and widely distributed gene delivery to the brain, as well as to other tissues, will be required. This project aims to compare the efficacy of these vectors in two different animal models of the mucopolysaccharidoses that exhibit a wide range of the clinical problems associated with these diseases, importantly including brain pathology.

粘多糖贮积症是一组遗传性疾病，对受影响的个体具有深远的影响。它们具有多效性，通常会导致过早死亡。尽管已经针对许多这些疾病开发了静脉内酶替代疗法，但这种治疗方法是侵入性的、非常昂贵、功效有限，并且在治疗脑病理学方面完全无效。其主要原因是大脑的受保护性质，它阻止静脉注射的酶进入。因此，必须考虑替代疗法，以便为粘多糖贮积症提供更有效的治疗，尤其是那些具有显着脑部病理学的粘多糖贮积症。基因疗法就是这样的一种替代疗法，但这仍然面临着将治疗剂（在这种情况下是编码必需酶的基因）引入大脑的问题。该项目旨在对两种基因治疗载体在治疗粘多糖病中发现的病理学各方面的功效进行比较评估。这两种载体都具有能够有效地将基因传递到不同细胞类型并导致靶细胞稳定遗传修饰的特性，使其成为长期治疗的理想选择。然而，为了有效的基因治疗，需要将大量且广泛分布的基因递送到大脑以及其他组织。该项目旨在比较这些载体在两种不同粘多糖病动物模型中的功效，这些模型表现出与这些疾病相关的广泛临床问题，重要的是包括脑病理学。