ANIMAL MODEL FOR GENE THERAPY OF INHERITED DISORDERS

遗传性疾病基因治疗的动物模型

• 批准号: 2908668
• 负责人: GARY B BASKIN
• 金额: $ 57.5万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-15 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2908668
• 关键词: Krabbe's disease; Macaca mulatta; animal breeding; animal colony; assistive reproductive technique; disease /disorder model; electrophysiology; embryo /fetus monitoring; gene therapy; genetic disorder; magnetic resonance imaging; nonhuman therapy evaluation; polymerase chain reaction

The objectives of this grant are to maintain and propagate a colony of rhesus monkeys that are carriers of globoid cell leukodystrophy (GLD) and to characterize GLD as it occurs in homozygous affected individuals. The long-term goal of this project is to develop a nonhuman primate animal model for gene therapy of inborn errors of metabolism. This colony of rhesus monkeys is the only colony of nonhuman primates in the world in which an inherited lysosomal disorder has been recognized, propagated, and is available for study. No other nonhuman primate model is available in which to test the actual clinical effectiveness of various therapeutic interventions in animals with a genetic disease. There are 21 carrier monkeys in the colony. They will be socially housed and bred naturally or artificially. Fetal growth will be monitored by ultrasound. Before or after birth, infants will be diagnosed by biochemistry and polymerase chain reaction as homozygous normal, heterozygous carrier, or homozygous affected. Infants will be characterized clinically, behaviorally, neurophysiologically, pathologically, and by neuroimaging. These data will be used in future applications as a baseline against which to compare the effects of therapeutic interventions, particularly gene therapy. We believe the specific aims of this proposal span the interests of several NIH institutes. These include the NCRR (animal models, biotechnology), the NINDS (neurogenetic disorders of infancy and childhood), the NIDDKD (development of somatic gene therapy approaches for inborn metabolic diseases), and the NICHHD (therapeutics during pregnancy, developmental abnormalities). The ability to study the in vivo efficacy and safety of gene therapy protocols in a nonhuman primate animal model with a genetic disease will be a powerful tool for advancing the prospects of genetic medicine in humans.

该补助金的目的是维持和繁殖一群球形细胞脑白质营养不良（GLD）携带者恒河猴，并描述GLD在纯合子受影响个体中发生的特征。 本研究的长期目标是建立一种非人灵长类动物模型，用于先天性代谢缺陷的基因治疗。 这群恒河猴是世界上唯一一群非人灵长类动物，其中遗传性溶酶体疾病已被确认，繁殖，并可用于研究。 没有其他非人灵长类动物模型可用于测试各种治疗干预在患有遗传疾病的动物中的实际临床有效性。殖民地里有21只携带者。 他们将被社会圈养，自然或人工繁殖。 胎儿生长将通过超声监测。 出生前或出生后，婴儿将通过生物化学和聚合酶链反应诊断为纯合子正常、杂合子携带者或纯合子受累。 将对婴儿进行临床、行为、神经生理学、病理学和神经影像学表征。 这些数据将在未来的应用中用作比较治疗干预，特别是基因治疗效果的基线。我们相信，这项提案的具体目标涵盖了几个NIH研究所的利益。 这些包括NCRR（动物模型，生物技术），NINDS（婴儿和儿童神经遗传性疾病），NIDDKD（先天性代谢疾病的体细胞基因治疗方法的开发）和NICHHD（妊娠期间的治疗，发育异常）。在患有遗传疾病的非人灵长类动物模型中研究基因治疗方案的体内疗效和安全性的能力将是推进人类遗传医学前景的有力工具。