Bäumer Nicole, Berdel Wolfgang E, Bäumer Sebastian
Deparment of Medicine A, Hematology and Oncology, University Hospital Muenster , Albert-Schweitzer Campus 1, Muenster, DE 48149, Germany.
Mol Pharm. 2017 May 1;14(5):1339-1351. doi: 10.1021/acs.molpharmaceut.6b01039. Epub 2017 Feb 15.
RNA interference strategies offer an alternative to small molecular drug targeting. Small interfering RNA (siRNA) constitutes a class of molecules that allows the effective and specific inhibition of the biosynthesis of any protein. Indeed, siRNA have emerged as a major tool in molecular biology techniques and an important approach to identify suitable therapy targets in cancer. However, siRNA therapy approaches in vivo are scarce. Two major problems hinder siRNA as a therapeutic tool: (1) delivery through the bloodstream leads to degradation or rapid renal clearance (stabilization) and (2) specific uptake by the desired cell type (specificity). This review summarizes the ongoing attempts to use RNAi against disease-causing factors. We compare methods to stabilize siRNA in different conjugates and that decorate these complexes with targeting molecules such as antibodies, single-chain Fv or Fab fragments, to enable specific uptake of the carriers by the respective cells. We propose the development of antibody-coupled siRNA complexes, which have shown to allow stabilization as well as targeted uptake of siRNA to cancer cells.
RNA干扰策略为小分子药物靶向治疗提供了一种替代方法。小干扰RNA（siRNA）是一类能够有效且特异性抑制任何蛋白质生物合成的分子。事实上，siRNA已成为分子生物学技术中的一种主要工具，也是在癌症中识别合适治疗靶点的重要方法。然而，体内siRNA治疗方法却很稀缺。有两个主要问题阻碍了siRNA成为一种治疗工具：（1）通过血液循环递送会导致降解或快速经肾清除（稳定性），以及（2）被所需细胞类型特异性摄取（特异性）。本综述总结了目前利用RNA干扰针对致病因子的尝试。我们比较了在不同缀合物中稳定siRNA以及用抗体、单链Fv或Fab片段等靶向分子修饰这些复合物的方法，以使载体能够被相应细胞特异性摄取。我们提议开发抗体偶联的siRNA复合物，其已显示能够实现siRNA的稳定以及对癌细胞的靶向摄取。
