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Optimization of cationic lipid-mediated gene transfer to airway epithelia
Journal article   Peer reviewed

Optimization of cationic lipid-mediated gene transfer to airway epithelia

A J Fasbender, J Zabner and M J Welsh
The American journal of physiology, Vol.269(1 Pt 1), pp.L45-L51
07/1995
DOI: 10.1152/ajplung.1995.269.1.L45
PMID: 7631813

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Abstract

The use of cationic lipids for gene transfer to airway epithelia has shown promise in in vitro and in vivo studies. However, previous studies have used a wide variety of different lipid preparations and different formulations. Few studies have been designed to optimize the variables involved in transfection, and none have been focused on airway epithelia. Therefore we examined variables that affect cationic lipid-mediated transfection of HeLa cells and of airway epithelial cells grown on permeable filter supports at the air-liquid interface. To quantitate expression of cDNA, we assayed expression of luciferase. We found that the ratio of DNA to lipid was an important variable that determined transfection efficiency. In both HeLa and airway epithelial cells, the optimum charge ratio of cationic lipid to anionic DNA was approximately 1.25, consistent with the notion that a positively charged complex facilitates interaction with the negatively charged cell membrane. After testing a series of readily available cationic lipids, we found that 1,2-dimyristyloxypropyl-N,N-dimethyl-hydroxyethyl ammonium bromide (DMRIE)/dioleoyl phosphatidylethandamine (DOPE) appeared to show good efficacy. The concentration of DNA and cationic lipid also played an important role: in HeLa cells the optimum concentration of cationic lipid was approximately 5 microM and in airway epithelial cells was approximately 15 microM.
Gene Transfer Techniques Luciferases - metabolism Trachea - cytology Cations - metabolism Humans Lipids - physiology Epithelial Cells DNA - metabolism Myristic Acids - pharmacology Transfection Phosphatidylethanolamines - pharmacology Trachea - physiology Epithelium - physiology HeLa Cells Quaternary Ammonium Compounds - pharmacology

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