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 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.
Deparment of Medicine A, Hematology and Oncology, University Hospital Muenster , Albert-Schweitzer Campus 1, Muenster, DE 48149, Germany.
Nicole
N
Bäumer
Deparment of Medicine A, Hematology and Oncology, University Hospital Muenster , Albert-Schweitzer Campus 1, Muenster, DE 48149, Germany.
Wolfgang E
WE
Berdel
Deparment of Medicine A, Hematology and Oncology, University Hospital Muenster , Albert-Schweitzer Campus 1, Muenster, DE 48149, Germany.
Sebastian
0000-0002-2790-1410
S
Bäumer
D000906:Antibodies / Q000737:chemistry*; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry
D000906:Antibodies; D007140:Immunoglobulin Fab Fragments; D034741:RNA, Small Interfering
bioconjugate therapeutics; siRNA; specificity; stabilization; therapeutic antibodies