Improved cationic lipid formulations for in vivo gene therapy
| Autor: | Marston Manthorpe, Loretta Sukhu, Carl J. Wheeler, Philip L. Felgner, Yali J. Tsai, Seng H. Cheng, John Marshall |
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| Rok vydání: | 1995 |
| Předmět: |
Chloramphenicol O-Acetyltransferase
Macromolecular Substances Recombinant Fusion Proteins Genetic Vectors DNA Recombinant Gene delivery Transfection General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Mice Plasmid History and Philosophy of Science In vivo Genes Reporter Cations Animals Cation Exchange Resins Enhancer Luciferases Reporter gene Drug Carriers Mice Inbred BALB C Chemistry General Neuroscience Drug Administration Routes Phosphatidylethanolamines Genetic Therapy beta-Galactosidase Lipids Cell biology Quaternary Ammonium Compounds Lipofectamine Naked DNA Dodecanol Liposomes Myristic Acids DNA |
| Zdroj: | Annals of the New York Academy of Sciences. 772 |
| ISSN: | 0077-8923 |
| Popis: | The problem of assessing in vivo activity of gene delivery systems is complex. The reporter gene must be carefully chosen depending on the application. Plasmids with strong promoters, enhancers and other elements that optimize transcription and translation should be employed, such as the CMVint and pCIS-CAT constructs. Formulation aspects of cationic lipid-DNA complexes are being studied in several laboratories, and the physical properties and molecular organization of the complexes are being elucidated. Likewise, studies on the mechanism of DNA delivery with cationic lipids are accumulating which support the basic concept that the complexes fuse with biological membranes leading to the entry of intact DNA into the cytoplasm. Naked plasmid DNA administered by various routes is expressed at significant levels in vivo. This observation is not restricted to skeletal and heart muscle, but has been observed in lung, dermis, and in undefined tissues following intravenous administration. Most of the widely available cationic lipids, including Lipofectin, Lipofectamine and DC-cholesterol have a very poor ability to enhance DNA expression above the baseline naked DNA level, at least in lung. In this report we have revealed a novel cationic lipid, DLRIE, which can significantly enhance CAT expression in mouse lung by 25-fold above the naked DNA level. Other compounds are currently being evaluated which can enhance the naked DNA expression even higher. Plasmid vector improvements have led to further increase in in vivo lung expression, so that the net improvement is > 5,000-fold. Results of this nature are advancing the pharmaceutical gene therapy opportunities for synthetic cationic lipid based gene delivery systems. |
| Databáze: | OpenAIRE |
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