Woessmann Willi, Damm-Welk Christine, Fuchs Uta, Borkhardt Arndt
Dept. of Pediatric Hematology and Oncology, Justus-Liebig-University, 35385 Giessen, Germany.
Rev Clin Exp Hematol. 2003 Sep;7(3):270-91.
Nucleic acid-based sequence-specific therapeutic intervention offers the potential for treatment of particular cancers without side effects. RNA interference (RNAi) induced by small interfering RNA (siRNA) (19-21 bp) is a normal cellular mechanism leading to highly specific and extraordinarily efficient degradation of the corresponding mRNA. The mechanism of RNAi as well as strategies for the design and delivery of siRNA are described. The growing role of RNAi in target validation for cancer-specific genetic aberrations is discussed. We attempt an early assessment of the potential for using RNAi technologies to treat cancer directly, especially hematologic malignancies. Promising targets for specific gene silencing in hematologic oncology include oncogenic fusion proteins and oncogenes activated by point mutations. Potency and specificity of gene silencing are the major advantages of the new RNAi technology over other nucleic acid-based gene targeting approaches. Crucial questions for pharmaceutical interventions remain. Advances in the areas of delivery, systemic spreading and duration of the silencing effect are necessary before the methodology can enter clinical oncology.
基于核酸的序列特异性治疗干预为治疗特定癌症且无副作用提供了可能性。由小干扰RNA（siRNA，19 - 21个碱基对）诱导的RNA干扰（RNAi）是一种正常的细胞机制，可导致相应mRNA的高度特异性和极其高效的降解。本文描述了RNAi的机制以及siRNA的设计和递送策略。讨论了RNAi在癌症特异性基因畸变的靶点验证中日益重要的作用。我们尝试对直接使用RNAi技术治疗癌症，尤其是血液系统恶性肿瘤的潜力进行早期评估。血液肿瘤学中特异性基因沉默的有前景的靶点包括致癌融合蛋白和由点突变激活的癌基因。基因沉默的效力和特异性是新RNAi技术相对于其他基于核酸的基因靶向方法的主要优势。药物干预仍存在关键问题。在该方法能够进入临床肿瘤学之前，在递送、全身扩散和沉默效应持续时间等方面取得进展是必要的。
