4.7 Review

Immunoprotein-Mediated siRNA Delivery

期刊

MOLECULAR PHARMACEUTICS
卷 14, 期 5, 页码 1339-1351

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.6b01039

关键词

siRNA; biaccnjugate therapeutics; stabilization; specificity; therapeutic antibodies

资金

  1. Wilhelm Sander Stiftung grant [2009.041.2, 2014.054.1, 2010.015.1]
  2. Deutsche Forschungsgemeinschaft [DFG EXC 1003]
  3. Deutsche Krebshilfe [70112282]
  4. Innovative Medical Research of the University of Munster Medical School (IMF) grant [111418, 211502, 121314, 111501]
  5. Medical Faculty, University of Munster

向作者/读者索取更多资源

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.

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