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• W2051269325 abstract "Gene therapy promises to revolutionize medicine by providing a method to treat diseases at their core level-the living cell-with the ultimate drug-the DNA. However, its success relies on designing transfection systems that can overcome the different delivery barriers present in living organisms. Viral vectors are the most efficient, but they are hampered by safety issues related to their immunogenicity and sometimes fatal toxicity. Synthetic non-viral vectors-cationic lipids, polymers and related gemini surfactants and oligomeric polycations provide promising alternatives to the use of viruses for delivering genes therapeutically, but their efficiency must be increased [1]. Heterocyclic cationic lipids in particular were shown to display a good transfection profile and low cytotoxic side effects. Our strategy [2] for generating new synthetic cationic vectors for gene delivery bearing pyridinium polar heads is based on the use of highly reactive pyrylium salts, which can react with a primary amine to generate the polar head in single high-yield step. Switching from a monoamine to a di- or polyamine one can readily access the classes of cationic lipids, gemini surfactants or lipophilic polycations. We present a structure-activity relationship study which identified several lead compounds such as 1–7 that display better transfection profiles than commercial transfection systems in vitro and in vivo. The study offers insights on the influence of the structural elements on the physico-chemical properties and transfection efficiency of these classes on non-viral transfection systems, as well as the optimum formulations found to be the most efficient on various tumor cell lines, as well as for in vivo studies. The advantages of the present technology to generate fluorescent molecular markers will also be discussed. 1. M. A. Ilies, W. A. Seitz, A. T. Balaban, Curr. Pharm. Design, 2002, 8, 2441–2473; D. Niculescu-Duvaz, J. Heyes, C. J. Springer, Curr. Med. Chem.2003, 10, 1233–1261; A. J. Kirby et al. Angew. Chem. Int. Ed.2003, 42, 1448–1457; M. E. Davis, Curr. Opin. Biotechnol.2002, 13, 128–131; K. Kostarelos, A. D. Miller, Adv. Genetics2005, 53, 71–118. 2. M. A. Ilies, W. A. Seitz, M. T. Caproiu, M. Wentz, R. E. Garfield, A. T. Balaban, Eur. J. Org. Chem.2003, 2645–2655; M. A. Ilies, W. A. Seitz, I. Ghiviriga, B. H. Johnson, A. Miller, E. B. Thompson, A. T. Balaban, J. Med. Chem.2004, 47, 3744–3754; M. A. Ilies, B. H. Johnson, F. Makori, A. Miller, W. A. Seitz, E. B. Thompson, A. T. Balaban, Arch. Biochem. Biophys.2005, 435, 217–226; A. T. Balaban, W. A. Seitz, M. A. Ilies, E. B. Thompson, R. E. Garfield, B. H. Johnson, A. Miller, M. Wentz, U.S. Patent 20050196863 A1." @default.
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• W2051269325 date "2006-01-01" @default.
• W2051269325 modified "2023-09-24" @default.
• W2051269325 title "178. Structure-Activity Relationships in a Library of Pyridinium Non-Viral Vectors for Gene Delivery" @default.
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• W2051269325 doi "https://doi.org/10.1016/j.ymthe.2006.08.202" @default.
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