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Supramolecular assemblies in functional siRNA delivery: Where do we stand?

Paper ID Volume ID Publish Year Pages File Format Full-Text
6996 527 2012 24 PDF Available
Title
Supramolecular assemblies in functional siRNA delivery: Where do we stand?
Abstract

The discovery of RNA interference (RNAi) has excited the scientific field due to its potential for wide range of therapeutic applications. The pharmacological mediator of RNAi, short interfering RNA (siRNA), however, has faced significant obstacles in reaching its target site and effectively exerting its silencing activity. Effective pharmacological use of siRNA requires ‘carriers’ that can deliver the siRNA to its intended site of action. The carriers assemble the siRNA into supramolecular complexes that display functional properties during the delivery process. This review will summarize non-viral approaches to siRNA delivery, emphasizing the current obstacles to delivery and the mechanisms employed to overcome these obstacles. The carriers successfully pursued in pre-clinical (animal) models will be presented so as to provide a glimpse of possible candidates for clinical testing. Supramolecular assembly of nucleic acids with carriers will be probed from thermodynamics and computational perspectives to understand supramolecular structures and their dynamics. The delivery and trafficking requirements for siRNA are then dissected and engineering approaches to overcoming these barriers will be articulated. The latter has been attempted both at the cellular levels, focusing on intracellular barriers, as well as systemic level, emphasizing macroscopic challenges affecting siRNA delivery. Clinical experience with non-viral siRNA delivery is summarized, highlighting the nature delivery modes attempted in clinical settings. We conclude with a perspective on the future of siRNA therapeutics, specifically concentrating on the possible impact of non-viral carriers in the field.

Keywords
Supramolecules; Short interfering RNA (siRNA); Non-viral delivery; Intracellular trafficking; Targeting; Clinical trialsRES, Reticuloendothelial system; IV, Intravenous; siRNA, Small interfering RNA; RNAi, RNA interference; PEG, Polyethyleneglycol; MW, Mo
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 8, March 2012, Pages 2546–2569
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us