Kren Betsy T, Chowdhury Namita Roy, Chowdhury Jayanta Roy, Steer Clifford J
Department of Medicine, University of Minnesota School of Medicine, Minneapolis, MN 55455, USA.
Liver Transpl. 2002 Dec;8(12):1089-108. doi: 10.1053/jlts.2002.36844.
Liver transplantation has become a well-recognized therapy for hepatic failure resulting from acute or chronic liver disease. It also plays a role in the treatment of certain inborn errors of metabolism that do not directly injure the liver. In fact, the liver maintains a central role in many inherited and acquired genetic disorders. There has been a considerable effort to develop new and more effective gene therapy approaches, in part, to overcome the need for transplantation as well as the shortage of donor livers. Traditional gene therapy involves the delivery of a piece of DNA to replace the faulty gene. More recently, there has been a growing interest in the use of gene repair to correct certain genetic defects. In fact, targeted gene repair has many advantages over conventional replacement strategies. In this review, we will describe a variety of viral and nonviral strategies that are now available to the liver. The ever-growing list includes viral vectors, antisense and ribozyme technology, and the Sleeping Beauty transposon system. In addition, targeted gene repair with RNA/DNA oligonucleotides, small-fragment homologous replacement, and triplex-forming and single-stranded oligonucleotides is a long-awaited and potentially exciting approach. Although each method uses different mechanisms for gene repair and therapy, they all share a basic requirement for the efficient delivery of DNA.
肝移植已成为治疗急性或慢性肝病所致肝衰竭的一种公认疗法。它在治疗某些不直接损伤肝脏的先天性代谢缺陷中也发挥着作用。事实上，肝脏在许多遗传性和获得性遗传疾病中都起着核心作用。人们一直在努力开发新的、更有效的基因治疗方法，部分原因是为了克服移植需求以及供肝短缺的问题。传统的基因治疗是通过递送一段DNA来替代有缺陷的基因。最近，人们对使用基因修复来纠正某些基因缺陷的兴趣日益浓厚。事实上，靶向基因修复比传统的替代策略有许多优势。在这篇综述中，我们将描述目前可用于肝脏的多种病毒和非病毒策略。不断增加的策略包括病毒载体、反义技术和核酶技术，以及“睡美人”转座子系统。此外，用RNA/DNA寡核苷酸、小片段同源替换、三链形成寡核苷酸和单链寡核苷酸进行靶向基因修复是一种期待已久且可能令人兴奋的方法。尽管每种方法使用不同的基因修复和治疗机制，但它们都对DNA的有效递送有一个基本要求。
