Scherr Michaela, Eder Matthias
Hannover Medical School, Department of Hematology and Oncology, Carl-Neuberg Strasse 1, D-30623 Hanover, Germany.
Curr Opin Mol Ther. 2004 Apr;6(2):129-35.
There has been a lack of powerful tools for systematic analysis of mammalian gene function, but RNA interference (RNAi) may now provide such a strategy. Stable transcription of RNAi triggers from suitable expression cassettes integrated into the host cell genome by viral gene transfer can induce long-term and heritable gene silencing in mammalian cells. However, the use of RNAi as a genetic tool is limited by difficulties in identifying efficient RNAi triggers, the problem of effective delivery and off-target effects, as well as potential genotoxic side effects of viral gene transfer strategies. Recent insights into the molecular mechanisms of silencing processes mediated by either siRNA or miRNA will allow further optimization of RNAi triggers as genetic tools.
一直以来,缺乏用于系统分析哺乳动物基因功能的强大工具,但RNA干扰(RNAi)现在可能提供这样一种策略。通过病毒基因转移将RNAi触发因子整合到宿主细胞基因组中,从合适的表达盒中稳定转录,可以在哺乳动物细胞中诱导长期且可遗传的基因沉默。然而,RNAi作为一种遗传工具的应用受到多种限制,包括难以鉴定有效的RNAi触发因子、有效递送问题和脱靶效应,以及病毒基因转移策略潜在的基因毒性副作用。最近对由siRNA或miRNA介导的沉默过程分子机制的深入了解,将有助于进一步优化RNAi触发因子作为遗传工具。