Kiwaki K, Matsuda I
Department of Pediatrics, Kumamoto University School of Medicine, Japan.
Acta Paediatr Jpn. 1996 Apr;38(2):189-92. doi: 10.1111/j.1442-200x.1996.tb03467.x.
Ornithine transcarbamylase (OTC) deficiency in humans is the most common and severe inborn error of the urea cycle. Despite therapeutic advances, OTC deficiency remains without adequate treatment, hence mortality rates are high. In the two available strains of OTC-deficient murine models, spf and spfash, researchers have tried to make genetic corrections by introducing the OTC gene. Transient but complete recovery of OTC was obtained in adult spfash mice and in OTC-deficient human primary hepatocytes, using a recombinant adenoviral vector. These experiments represent a first step in the development of human gene therapy for OTC deficiency and other hepatic enzyme deficiencies.
人类鸟氨酸转氨甲酰酶（OTC）缺乏症是尿素循环中最常见且最严重的先天性代谢缺陷。尽管治疗取得了进展，但OTC缺乏症仍未得到充分治疗，因此死亡率很高。在两种可用的OTC缺陷小鼠模型品系spf和spfash中，研究人员试图通过引入OTC基因进行基因校正。使用重组腺病毒载体，在成年spfash小鼠和OTC缺陷的人类原代肝细胞中获得了OTC的短暂但完全恢复。这些实验代表了针对OTC缺乏症和其他肝酶缺乏症的人类基因治疗发展的第一步。
