Gene Therapy for Urea Cycle Disorders

描述（由申请人提供）：本申请的目的是开发一种有效的鸟氨酸转氨甲酰酶（OTC）缺乏症的基因疗法。 研究开始是开发最佳AAV载体，在项目I中称为“临床候选物”。 本项目还将进行其他研究，以评估成功的肝定向基因治疗的潜在免疫屏障。 在项目II中，将在OTC缺陷小鼠和非人灵长类动物中评价临床候选药物的安全性和疗效。 项目III将研究载体基因组的分子状态及其潜在致癌性。 用于载体生产、细胞形态学、动物模型和管理的核心将为这些项目提供支持。 将召集一个外部科学咨询委员会和一个伦理咨询委员会，为项目领导提供建议。 在这个为期四年的项目完成后，研究人员希望提供具有临床前数据的AAV载体，以支持其翻译成人类。

DESCRIPTION (provided by applicant): The goal of this application is to develop an effective gene therapy for ornithine transcarbamylase (OTC) deficiency. Studies begin with the development of an optimal AAV vector called the "clinical candidate" in Project I. Additional studies will be performed in this project to evaluate potential immunologic barriers to successful liver directed gene therapy. The clinical candidate will be evaluated for safety and efficacy in OTC deficient mice and nonhuman primates in Project II. The molecular state of the vector genome and its potential oncogenicity will be studied in Project III. Cores for vector production, cell morphology, animal models, and administration will provide support to the projects. An External Scientific Advisory Committee and an Ethics Advisory Board will be convened to provide advice to the program leadership. At the completion of this four year program, the investigators hope to provide an AAV vector with preclinical data to support its translation into humans.