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Genetic pharmacology: progresses in siRNA delivery and therapeutic applications

Gene Therapy volume 24, pages 151–156 (2017)Cite this article

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Abstract

In the RNA interference process, the catalytic degradation of an endogenous mRNA results from the Watson-Crick complementary recognition by either a small silencing synthetic double-stranded ribonucleotide (siRNA) or by a small hairpin RNA (shRNA) produced in the cell by transcription from a DNA template. This interference process ideally results in an exquisitely specific mRNA suppression. The present review is dedicated to siRNAs. It describes the mechanism of RNA silencing and the main siRNA delivery techniques, with a focus on siRNA self-complexing to cationic lipids to form nanoparticles, which are called lipoplexes. The addition to lipoplexes of an anionic polymer leads to the ternary formulation APIRL (Anionic-Polymer-Interfering-RNA-Lipoplexes) with increased in vivo stability and biological efficacy. In terms of clinical development, the review focuses on therapeutic applications by intravenous delivery to the liver and inflammatory joints, and to localized siRNA delivery to the ocular sphere.

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Authors and Affiliations

  1. CNRS, UTCBS UMR 8258, Paris, France

    D Scherman, A Rousseau, P Bigey & V Escriou

  2. Université Paris Descartes, Faculty of Pharmacy, Sorbonne-Paris-Cité, UTCBS, Paris, France

    D Scherman, A Rousseau, P Bigey & V Escriou

  3. Chimie ParisTech, PSL Research University, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS), Paris, France

    D Scherman, A Rousseau, P Bigey & V Escriou

  4. INSERM, UTCBS U 1022, F-75006 Paris, France, 4,avenue de l’Observatoire, Paris, France

    D Scherman, A Rousseau, P Bigey & V Escriou

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  1. D Scherman
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  2. A Rousseau
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  3. P Bigey
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Corresponding author

Correspondence to D Scherman.

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Competing interests

DS, VE and PB are coauthors of the patent protecting the APIRL formulations: US 2012093915, Vectors including an anionic macromolecule and a cationic lipid for delivering small nucleic acids. The remaining author declares no conflict of interest.

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Scherman, D., Rousseau, A., Bigey, P. et al. Genetic pharmacology: progresses in siRNA delivery and therapeutic applications. Gene Ther 24, 151–156 (2017). https://doi.org/10.1038/gt.2017.6

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