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siRNA and RNAi optimization

AutorAlagia, Adele; Eritja Casadellà, Ramón
Palabras claveRNAi
siRNA
miRNA
RISC
Ago2
Off-target effects
chemical modification
structural modification
exosomes
delivery
RNA microsponges
HDL-like particles
dumbbell
si-siRNA
aiRNA
asiRNA
is-siRNA
dsi-RNA
ss-siRNA
Fecha de publicación2-feb-2016
EditorJohn Wiley & Sons
CitaciónWiley Interdisciplinary Reviews- RNA
ResumenThe discovery and examination of the posttranscriptional gene regulatory mechanism known as RNA interference (RNAi) contributed to the identification of small interfering RNA (siRNA) and the comprehension of its enormous potential for clinical purposes. Theoretically, the ability of specific target gene downregulation makes the RNAi pathway an appealing solution for several diseases. Despite numerous hurdles resulting from the inherent properties of siRNA molecule and proper delivery to the target tissue, more than 50 RNA-based drugs are currently under clinical testing. In this work, we analyze the recent literature in the optimization of siRNA molecules. In detail, we focused on describing the most recent advances of siRNA field aimed at optimize siRNA pharmacokinetic properties. Special attention has been given in describing the impact of RNA modifications in the potential off-target effects (OTEs) such as saturation of the RNAi machinery, passenger strand-mediated silencing, immunostimulation, and miRNA-like OTEs as well as to recent developments on the delivery issue. The novel delivery systems and modified siRNA provide significant steps toward the development of reliable siRNA molecules for therapeutic use. © 2016 Wiley Periodicals, Inc.
Versión del editorhttp://dx.doi.org/10.1021/10.1002/wrna.1337
URIhttp://hdl.handle.net/10261/131031
DOI10.1002/wrna.1337
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