Cation substitution in cationic phosphonolipids: a new concept to improve transfection activity and decrease cellular toxicity
| Autor: | Herve Des Abbayes, Anne Hervé, Virginie Floch, Claude Ferec, Jean Jacques Yaouanc, Jean Claude Clement, Séverine Loisel, Erwann Guénin |
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| Přispěvatelé: | Chimie, Electrochimie Moléculaires et Chimie Analytique (CEMCA), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC) |
| Rok vydání: | 2000 |
| Předmět: |
Stereochemistry
Genetic Vectors Phospholipid Gene delivery 010402 general chemistry Transfection 01 natural sciences Cell Line chemistry.chemical_compound Mice Structure-Activity Relationship Genes Reporter Cations Drug Discovery [CHIM]Chemical Sciences Animals Humans Aspartate Aminotransferases Luciferases Phospholipids 010405 organic chemistry Chemistry Genetic transfer Cationic polymerization Gene Transfer Techniques Alanine Transaminase 0104 chemical sciences Luminescent Measurements Biophysics Molecular Medicine Female Drug carrier Linker DNA |
| Zdroj: | Journal of Medicinal Chemistry Journal of Medicinal Chemistry, American Chemical Society, 2000, 43, pp.4617--4628. ⟨10.1021/jm000006z⟩ |
| ISSN: | 0022-2623 1520-4804 |
| DOI: | 10.1021/jm000006z⟩ |
| Popis: | International audience; Cationic lipids have been shown to be an interesting alternative to viral vector-mediated gene delivery into in vitro and in vivo model applications. Prior studies have demonstrated that even minor structural modifications of the lipid hydrophobic domain or of the lipid polar domain result in significant changes in gene delivery efficiency. Previously, we developed a novel class of cationic lipids called cationic phosphonolipids and described the ability of these vectors to transfer DNA into different cell lines and in vivo. Up until now, in all new cationic lipids, nitrogen atoms have always carried the cationic or polycationic charge. Recently we have developed a new series of cationic phosphonolipids characterized by a cationic charge carried by a phosphorus or arsenic atom. In a second step, we have also examined the effects of the linker length between the cation and the hydrophobic domain as regards transfection activity. Transfection activities of this library of new cationic phosphonolipids were studied in vitro in different cell lines (HeLa, CFT1, K562) and in vivo using a luciferase reporter gene. A luminescent assay was carried out to assess luciferase expression. We demonstrated that cation substitution on the polar domain of cationic phosphonolipids (N → P or As) results in significant increase in transfection activity for both in vitro and in vivo assays and decrease of cellular toxicity. |
| Databáze: | OpenAIRE |
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