METHOD FOR INCREASING GENE THERAPY EFFICACY AND SAFETY

提高基因治疗功效和安全性的方法

• 批准号: 6486229
• 负责人: JULIAN DAVID DOWN
• 金额: $ 10万
• 依托单位: BIOTRANSPLANT, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6486229
• 关键词: autologous transplantation; biotechnology; diagnosis procedure safety; evaluation /testing; gene therapy; green fluorescent proteins; immune tolerance /unresponsiveness; laboratory mouse; technology /technique development

DESCRIPTION (provided by the applicant): The aim of this proposal is to develop a non-myeloablative conditioning protocol with increased safety and efficacy for the induction of specific immune tolerance to genetically modified cells. Potential applications of gene therapy in the treatment of genetic and autoimmune disorders are widespread, but progress has suffered from a severe reduction in efficacy due to immune reactions raised against therapeutic transgene products. Induction of specific immune tolerance through mixed hematopoietic chimerism is an established methodology that can effectively re-educate the immune system to eliminate immune rejection. To achieve engraftment of allogeneic stem cells, conditioning requirements are associated with toxicities, and graft-versus-host disease is a common side effect. Studies have shown that molecular chimerism can be used to induce tolerance. Our preliminary data suggest that specific immune tolerance can be induced to a single immunogenic protein expressed on autologous cells, and that conditioning requirements for transplantation of molecularly modified autologous cells are less than those required for allogeneic transplants. We believe that the effectiveness of gene therapy can be greatly improved by inducing specific immune tolerance to foreign proteins to be transferred and that this can be accomplished using non-toxic protocols.

描述（由申请人提供）：本提案的目的是开发 安全性和有效性增加的非清髓性预处理方案 用于诱导对遗传修饰细胞的特异性免疫耐受。 基因治疗在遗传性和 自身免疫性疾病是普遍存在的，但进展受到了严重的 由于针对治疗药物的免疫反应而导致疗效降低 转基因产品通过混合免疫诱导特异性免疫耐受 造血嵌合体是一种已建立的方法， 重新训练免疫系统以消除免疫排斥。实现 同种异体干细胞的植入，调节要求与 具有毒性，并且移植物抗宿主病是常见的副作用。研究 已经表明分子嵌合体可以用来诱导耐受性。我们 初步数据表明，可以诱导特异性免疫耐受， 在自体细胞上表达单一免疫原性蛋白质， 移植分子修饰的自体细胞的要求是 少于同种异体移植所需的量。我们认为 基因治疗的有效性可以通过诱导特异性的 对待转移的外源蛋白质的免疫耐受性， 使用无毒协议完成。