Liposome mediated gene transfer into GH3 cells, and rat brain, liver and gut: comparison of different polar or aliphatic domains.
BACKGROUND
Cationic liposomes may be used in gene transfer. However, different liposome configurations have varying efficiency in different tissues.


OBJECTIVE
To compare multiple lipids during gene transfer into the intestinal mucosa, liver and central nervous system in the adult rat. We evaluate different lipid aliphatic and polar head domains.


METHODS
Nine cationic or neutral phospholipids, combined with a cationic cholesterol derivative, have been compared to Lipofectin. Transfection was into GH3 cells and the adult rat brain, liver or intestinal mucosa. Results Optimum DNA:lipid ratio was lowest (1:2) in the intestinal mucosa and highest in GH3 cells (1:40). Lipofectin ", was most effective in brain and GH3 cells but had no activity in intestinal mucosa. Saturated cationic lipids transfect differently in GH3 cells and GI mucosa than in liver and brain. However, with saturated neutral phospholipids, GH3 cells, intestinal mucosa and liver transfect similarly. DOTAP the longest unsaturated cationic lipid (18:1) was most effective in the intestine, whereas DMEPC the shortest saturated neutral lipid (14:0) was optimal in the liver.


CONCLUSIONS
In this study we propose a rational approach, based on systematic variations of lipids, to optimize liposome mediated gene transfer into the ventricular system of the brain, the liver and gastro-intestinal tract in the adult rat. Additionally, we demonstrate the feasibility of gene transfer into the mucosal cells of the gastro-intestinal tract as well as throughout the ventricular system of the rat brain. This requires liposomes which contain a cationic cholesterol derivative.
Katsel
P L
PL
Department of Anesthesiology, The Mount Sinai School of Medicine CUNY, New York, NY, USA. pkatsel@earthlink.net
O'Connell
B
B
Mizuno
T M
TM
Mobbs
C V
CV
Greenstein
R J
RJ
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D002784:Cholesterol / Q000031:analogs & derivatives; D004247:DNA / Q000378:metabolism; D018014:Gene Transfer Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D050356:Lipid Metabolism; D008081:Liposomes; D008099:Liver / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D008081:Liposomes; D010714:Phosphatidylethanolamines; D010743:Phospholipids; C020888:1,2-dielaidoylphosphatidylethanolamine; D004247:DNA; D002784:Cholesterol; D008156:Luciferases