Immunoprotein-Mediated siRNA Delivery

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 tec...

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Bibliographic Details
Published in:Molecular pharmaceutics 2017-05, Vol.14 (5), p.1339-1351
Main Authors: Bäumer, Nicole, Berdel, Wolfgang E, Bäumer, Sebastian
Format: Article
Language:English
Subjects:
Antibodies - chemistry
Immunoglobulin Fab Fragments - chemistry
RNA Interference
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - chemistry
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Summary: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.
ISSN:1543-8384
1543-8392
DOI:10.1021/acs.molpharmaceut.6b01039