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LDLR-Mediated Targeting and Productive Uptake of siRNA-Peptide Ligand Conjugates In Vitro and In Vivo

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Broc, Baptiste | Varini, Karine | Sonnette, Rose | Pecqueux, Belinda | Benoist, Florian | Masse, Maxime | Mechioukhi, Yasmine | Ferracci, Géraldine | Temsamani, Jamal | Khrestchatisky, Michel | Jacquot, Guillaume | Lécorché, Pascaline

Edité par CCSD ; MDPI -

International audience. Small RNA molecules such as microRNA and small interfering RNA (siRNA) have become promising therapeutic agents because of their specificity and their potential to modulate gene expression. Any gene of interest can be potentially up- or down-regulated, making RNA-based technology the healthcare breakthrough of our era. However, the functional and specific delivery of siRNAs into tissues of interest and into the cytosol of target cells remains highly challenging, mainly due to the lack of efficient and selective delivery systems. Among the variety of carriers for siRNA delivery, peptides have become essential candidates because of their high selectivity, stability, and conjugation versatility. Here, we describe the development of molecules encompassing siRNAs against SOD1, conjugated to peptides that target the low-density lipoprotein receptor (LDLR), and their biological evaluation both in vitro and in vivo.

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