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Review
. 2019 Sep;14(5):497-510.
doi: 10.1016/j.ajps.2018.12.005. Epub 2019 Feb 13.

Design, mechanism, delivery and therapeutics of canonical and Dicer-substrate siRNA

Maria Abdul Ghafoor Raja  1 , Haliza Katas  2 , Muhammad Wahab Amjad  1
Affiliations
Review

Design, mechanism, delivery and therapeutics of canonical and Dicer-substrate siRNA

Maria Abdul Ghafoor Raja et al. Asian J Pharm Sci. 2019 Sep.

Abstract

Upon the discovery of RNA interference (RNAi), canonical small interfering RNA (siRNA) has been recognized to trigger sequence-specific gene silencing. Despite the benefits of siRNAs as potential new drugs, there are obstacles still to be overcome, including off-target effects and immune stimulation. More recently, Dicer substrate siRNA (DsiRNA) has been introduced as an alternative to siRNA. Similarly, it also is proving to be potent and target-specific, while rendering less immune stimulation. DsiRNA is 25-30 nucleotides in length, and is further cleaved and processed by the Dicer enzyme. As with siRNA, it is crucial to design and develop a stable, safe, and efficient system for the delivery of DsiRNA into the cytoplasm of targeted cells. Several polymeric nanoparticle systems have been well established to load DsiRNA for in vitro and in vivo delivery, thereby overcoming a major hurdle in the therapeutic uses of DsiRNA. The present review focuses on a comparison of siRNA and DsiRNA on the basis of their design, mechanism, in vitro and in vivo delivery, and therapeutics.

Keywords: Drug delivery system; Gene carrier; Gene silencing; Non-viral vector; Polymeric nanoparticles; RNA interference.

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Figures

Fig. 1.
Fig. 1
siRNA-mediated RNAi mechanism: siRNAs are formed from short hairpin RNAs and long dsRNAs after being processed by Dicer. (Reproduced with permission from . Copyright 2005 Elsevier B.V.).
Fig. 2.
Fig. 2
Mechanism of DsiRNA processing in mammalian systems. (Reproduced with permission from . Copyright 2005 Elsevier B.V.).
See this image and copyright information in PMC

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