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.

这笔赠款的目标是维持和传播一个恒河猴的殖民地，这些猴子是球形细胞白细胞营养不良（GLD）的载体，并表征GLD在纯合受影响的个体中发生的GLD。 该项目的长期目标是开发一种非人类灵长类动物模型，用于新陈代谢错误的基因治疗。 这种恒河猴的殖民地是世界上唯一的非人类灵长类动物的菌落，其中遗传性溶酶体疾病已被认可，传播并可以进行研究。 没有其他非人类灵长类动物模型可以在患有遗传疾病的动物中测试各种治疗干预措施的实际临床有效性。殖民地有21只载猴。 他们将在社会上自然或人工繁殖。 胎儿生长将通过超声监测。 出生前或之后，婴儿将通过生物化学和聚合酶链反应诊断为纯合正常，杂合载体或纯合子影响。 婴儿将在临床，行为，神经生理学，病理学和神经影像学上进行表征。 这些数据将在将来的应用中用作比较治疗干预措施（尤其是基因治疗）的影响的基线。我们认为，该提案的具体目的涵盖了几家NIH机构的利益。 其中包括NCRR（动物模型，生物技术），NIND（婴儿期和儿童的神经发生疾病），NIDDKD（用于先天代谢疾病的体细胞基因治疗方法的开发）和NICHHD（怀孕期间的疗法，发育异常，发育异常）。研究具有遗传疾病的非人类灵长类动物模型中基因治疗方案的体内功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。