Gene Therapy for Urea Cycle Disorders

描述(申请人提供)：本申请的目标是开发一种有效的鸟氨酸转氨酶(OTC)缺乏症的基因疗法。研究首先在项目I中开发一种名为“临床候选”的最佳AAV载体，在该项目中还将进行其他研究，以评估成功的肝脏导向基因治疗的潜在免疫障碍。项目二将对OTC缺陷小鼠和非人类灵长类动物进行安全性和有效性评估。项目三将研究载体基因组的分子状态及其潜在的致瘤性。载体生产、细胞形态、动物模型和管理的核心将为项目提供支持。将召集一个外部科学咨询委员会和一个道德咨询委员会，为项目领导提供建议。在这项为期四年的计划完成后，研究人员希望提供一种带有临床前数据的AAV载体，以支持其转化为人类。

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.