Erasmus MC-University Medical Center, Department of Surgery and Laboratory of Experimental Transplantation and Intestinal Surgery, Rotterdam, The Netherlands.
Expert Opin Biol Ther. 2011 Mar;11(3):315-27. doi: 10.1517/14712598.2011.548799. Epub 2011 Jan 5.
Diseases of the liver represent a major health problem. Often treatments are ineffective, prompting the need for new therapeutic strategies. From extensive preclinical studies, gene therapy in particular mediated by adeno-associated virus (AAV)-derived vectors, has now emerged as the prime candidate for clinical application. AAV-mediated gene therapy for inherited liver diseases has now become a clinical reality, in particular for the treatment of hemophilia B.
This review provides a summary of current literature on AAV-mediated gene therapies for both inherited and acquired liver diseases and outlines different strategies to overcome current clinical limitations. The unique properties of AAV over other viral vectors are highlighted as well as the current challenges which are faced for wide-ranging clinical application.
Despite the extensive positive results from animal models, successful application in clinical settings is hampered by immunological barriers. However, immune suppression and other strategies can be employed to overcome these limitations. Given some of their unique advantages, AAV vectors are currently the most obvious candidate for hepatic gene therapy applications, however, serotype-related issues of immune reactivity still represent a formidable barrier for clinical success.
肝脏疾病是一个主要的健康问题。通常，治疗效果不佳，这促使人们需要新的治疗策略。从广泛的临床前研究来看，腺相关病毒（AAV）衍生载体介导的基因治疗现在已经成为临床应用的主要候选者。AAV 介导的基因治疗现已成为治疗遗传性肝脏疾病的临床现实，特别是治疗乙型血友病。
本文综述了目前关于 AAV 介导的遗传性和获得性肝脏疾病的基因治疗的文献，并概述了克服当前临床限制的不同策略。强调了 AAV 相对于其他病毒载体的独特特性，以及广泛临床应用所面临的当前挑战。
尽管动物模型的结果非常积极，但在临床环境中的成功应用受到免疫障碍的阻碍。然而，可以采用免疫抑制和其他策略来克服这些限制。鉴于它们的一些独特优势，AAV 载体目前是肝脏基因治疗应用的最明显候选者，但是，血清型相关的免疫反应问题仍然是临床成功的一个巨大障碍。
