| Autor: |
Habrant D; In-Cell-Art , 21 rue de la Noue Bras de Fer, 44200 Nantes, France., Peuziat P; Unité INSERM UMR1087, CNRS UMR 6291 , 8 quai Moncousu, 44007 Nantes, France.; Université de Nantes , L'institut du Thorax, 8 quai Moncousu, 44007 Nantes, France., Colombani T; Unité INSERM UMR1087, CNRS UMR 6291 , 8 quai Moncousu, 44007 Nantes, France.; Université de Nantes , L'institut du Thorax, 8 quai Moncousu, 44007 Nantes, France., Dallet L; CBMN UMR-CNRS 5248 IECB, Université de Bordeaux 1-IPB , Allée Geoffroy Saint Hilaire, Pessac F-33600, France., Gehin J; In-Cell-Art , 21 rue de la Noue Bras de Fer, 44200 Nantes, France., Goudeau E; In-Cell-Art , 21 rue de la Noue Bras de Fer, 44200 Nantes, France., Evrard B; In-Cell-Art , 21 rue de la Noue Bras de Fer, 44200 Nantes, France., Lambert O; CBMN UMR-CNRS 5248 IECB, Université de Bordeaux 1-IPB , Allée Geoffroy Saint Hilaire, Pessac F-33600, France., Haudebourg T; Unité INSERM UMR1087, CNRS UMR 6291 , 8 quai Moncousu, 44007 Nantes, France.; Université de Nantes , L'institut du Thorax, 8 quai Moncousu, 44007 Nantes, France., Pitard B; In-Cell-Art , 21 rue de la Noue Bras de Fer, 44200 Nantes, France.; Unité INSERM UMR1087, CNRS UMR 6291 , 8 quai Moncousu, 44007 Nantes, France.; Université de Nantes , L'institut du Thorax, 8 quai Moncousu, 44007 Nantes, France. |
| Abstrakt: |
The intracellular delivery of nucleic acid molecules is a complex process involving several distinct steps; among these the endosomal escape appeared to be of particular importance for an efficient protein production (or inhibition) into host cells. In the present study, a new series of ionizable vectors, derived from naturally occurring aminoglycoside tobramycin, was prepared using improved synthetic procedures that allow structural variations on the linker and hydrophobic domain levels. Complexes formed between the new ionizable lipids and mRNA, DNA, or siRNA were characterized by cryo-TEM experiments and their transfection potency was evaluated using different cell types. We demonstrated that lead molecule 30, bearing a biodegradable diester linker, formed small complexes with nucleic acids and provided very high transfection efficiency with all nucleic acids and cell types tested. The obtained results suggested that the improved and "universal" delivery properties of 30 resulted from an optimized endosomal escape, through the lipid-mixing mechanism. |
