ABSTRACT
Introduction: The discovery of RNA interference (RNAi) earned the 2006 Nobel Prize in Physiology or Medicine for its biological significance and potential for developing novel therapeutics. The small interfering RNA (siRNA) is the most promising tool for translating RNAi to clinical use. Efforts are ongoing to improve siRNA delivery through developing novel biomaterials and delivery strategies. Given time, it appears that siRNA drugs will eventually become a reality.
Areas covered: The currently used approaches for siRNA delivery are discussed with a focus on siRNA therapeutics currently in clinical testing. A comparison of advantageous aspects of currently available platforms and the possibility of further optimization for increased efficiency and safety are presented. Future directions in siRNA delivery are also highlighted.
Expert opinion: The recent success in the field of siRNA delivery is based mainly on developing new biomaterials with extraordinarily high activities. Notably, the introduction of ionizable lipids and novel targeting ligands represent two huge steps for realizing siRNA therapy. The currently available systems are largely directed to the liver and the new challenge is to extend their applicability for treating diseases of other organs. Active targeting to different organs is the most promising approach for developing new siRNA-based therapeutics.
Article highlights
siRNA-based therapeutics have broad potential applications for treating various diseases even when systemically administered.
The key for successful siRNA therapy is the development of efficient delivery systems that specifically deliver siRNA to cells in sufficient levels to produce a therapeutic effect using a minimal dose.
The currently available techniques for siRNA delivery can be broadly classified into siRNA-bioconjugates and polymeric or lipidic NPs.
Optimization of siRNA delivery to target sites focuses mainly on increasing the stability of siRNA, improving tissue targeting and cellular uptake, and enhancing endosomal escape.
Active targeting to different organs is the most promising approach for developing siRNA-based therapeutics for organs other than the liver.
Future directions in siRNA delivery also include the use of multifunctional devices and combined therapy, exploring new targeting ligands and the design of smart stimuli-responsive systems.
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Acknowledgments
The authors thank Milton S. Feather for editing the English in this manuscript.
Disclousre statement
No potential conflict of interest was reported by the authors.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer Declarations
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.