Novel therapeutic strategies for clinical applications of intefering RNA

The regulation of gene expression has raised many hopes for the discovery of new therapeutic strategies. This is the case of small interfering RNA (siRNA) that can modulate the expression of various genes. However, despite their potential, siRNA are unstable in biological fluids. Moreover, due to their hydrophilicity and overall negative charge, these molecules must be chemically modified or addressed by nanotechnologies to be able to penetrate target cells and reach the cytoplasm to induce gene inhibition. Chemical modifications have been made to the basic structure of siRNA, which have unfortunately been accompanied by off-target effects. Lipid conjugates addressed to the liver or lipid nanotechnology with liver affinity are the most advanced systems in the clinic. This review focuses on these different strategies and highlights new and prospective approaches to address siRNA to other tissues of the body than the liver. (C) 2020 l'Academie nationale de medecine. Published by Elsevier Masson SAS. All rights reserved.