Junge Norman, Mingozzi Federico, Ott Michael, Baumann Ulrich
*Paediatric Gastroenterology and Hepatology, Children's Hospital, Hannover Medical School, Hannover, Germany †Genethon, Evry, France ‡Twincore, Centre for Experimental and Clinical Infection Research, Hannover, Germany.
J Pediatr Gastroenterol Nutr. 2015 Apr;60(4):433-40. doi: 10.1097/MPG.0000000000000703.
Liver-based metabolic diseases account for a substantial burden of childhood diseases. In most patients, treatment is often limited to supportive measures and liver transplantation is ultimately required. Even despite the excellent long-term outcome of liver transplantation, the procedure is associated with a significant morbidity and mortality. Gene therapy, in contrast, has great potential to save lives, improve the quality of life, and offer few risks and adverse effects compared with present therapies including liver transplantation. The most promising results to date in liver gene transfer have been achieved with adeno-associated virus. Although safety issues, such as immunogenicity of vector and/or transgene product, remain an important concern, gene therapy is ready for clinical trials in adults and adolescents. Developing and testing safe approaches for efficient and long-term stable applications in newborns and small children, such as targeted integration and gene correction, is one of the remaining future challenges.
基于肝脏的代谢性疾病构成了儿童疾病的重大负担。在大多数患者中，治疗往往仅限于支持性措施，最终需要进行肝移植。尽管肝移植具有出色的长期疗效，但该手术仍伴随着显著的发病率和死亡率。相比之下，基因治疗有很大潜力挽救生命、提高生活质量，并且与包括肝移植在内的现有疗法相比，风险和不良反应较少。迄今为止，在肝脏基因转移方面最有前景的结果是通过腺相关病毒实现的。尽管诸如载体和/或转基因产物的免疫原性等安全性问题仍然是一个重要关注点，但基因治疗已准备好在成人和青少年中进行临床试验。开发和测试在新生儿和幼儿中进行高效、长期稳定应用的安全方法，如靶向整合和基因校正，是未来剩下的挑战之一。
