A Cell‐Penetrating Foldamer with a Bioreducible Linkage for Intracellular Delivery of DNA |
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| Authors: | Dr. Céline Douat Dr. Christopher Aisenbrey Stéphanie Antunes Dr. Marion Decossas Dr. Olivier Lambert Dr. Burkhard Bechinger Dr. Antoine Kichler Dr. Gilles Guichard |
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| Affiliation: | 1. Univ. Bordeaux, CBMN, UMR 5248, Institut Européen de Chimie et Biologie (IECB), 2 rue Robert Escarpit, 33607 Pessac (France);2. CNRS, CBMN, UMR 5248, 33600 Pessac (France);3. Membrane Biophysics and NMR, Chemistry Institute, University of Strasbourg‐CNRS UMR7177, 4, Rue Blaise Pascal, 67008 Strasbourg (France);4. Univ. Bordeaux, CBMN, UMR 5248, All. Geoffroy Saint‐Hilaire, 33600 Pessac (France);5. Laboratoire “Vecteurs: Synthèse et Applications Thérapeutiques”, UMR 7199 CNRS—Université de Strasbourg, Labex Medalis, Faculté de Pharmacie, 74 route du Rhin, 67401 Illkirch cedex (France) |
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| Abstract: | Despite significant advances in foldamer chemistry, tailored delivery systems based on foldamer architectures, which provide a high level of control over secondary structure, are curiously rare among non‐viral technologies for transporting nucleic acids into cells. A potent pH‐responsive, bioreducible cell‐penetrating foldamer (CPF) was developed through covalent dimerization of a short (8‐mer) amphipathic oligourea sequence bearing histidine‐type units. This CPF exhibits a high capacity to assemble with pDNA and mediates efficient delivery of nucleic acids into the cell. Furthermore, it does not adversely affect cellular viability and was shown to compare favorably with a cognate peptide transfection agent based on His‐rich sequences. |
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| Keywords: | cell‐penetrating peptides disulfide‐mediated dimerization foldamers gene delivery transfection |
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