Ivics Zoltán, Izsvák Zsuzsanna
Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Curr Gene Ther. 2006 Oct;6(5):593-607. doi: 10.2174/156652306778520647.
Gene therapy is a promising strategy for the treatment of several inherited and acquired human diseases. Several vector platforms exist for the delivery of therapeutic nucleic acids into cells. Vectors based on viruses are very efficient at introducing gene constructs into cells, but their use has been associated with genotoxic effects of vector integration or immunological complications due to repeated administration in vivo. Non-viral vectors are easier to engineer and manufacture, but their efficient delivery into cells is a major challenge, and the lack of their chromosomal integration precludes long-term therapeutic effects. Transposable elements are non-viral gene delivery vehicles found ubiquitously in nature. Transposon-based vectors have the capacity of stable genomic integration and long-lasting expression of transgene constructs in cells. Molecular reconstruction of Sleeping Beauty, an ancient transposon in fish, represents a cornerstone in applying transposition-mediated gene delivery in vertebrate species, including humans. This review summarizes the state-of-the-art in the application of transposable elements for therapeutic gene transfer, and identifies key targets for the development of transposon-based gene vectors with enhanced efficacy and safety for human applications.
基因治疗是治疗多种遗传性和获得性人类疾病的一种很有前景的策略。存在几种用于将治疗性核酸递送至细胞的载体平台。基于病毒的载体在将基因构建体导入细胞方面非常有效，但其使用与载体整合的基因毒性作用或由于在体内重复给药引起的免疫并发症有关。非病毒载体更易于设计和制造，但其有效递送至细胞是一项重大挑战，并且它们缺乏染色体整合排除了长期治疗效果。转座元件是在自然界中普遍存在的非病毒基因递送载体。基于转座子的载体具有在细胞中稳定基因组整合和转基因构建体长期表达的能力。鱼类中的古老转座子——睡美人的分子重建，是在包括人类在内的脊椎动物物种中应用转座介导的基因递送的基石。本综述总结了转座元件在治疗性基因转移应用中的最新进展，并确定了开发具有更高疗效和安全性的用于人类应用的基于转座子的基因载体的关键靶点。
