Liposome-complexed adenoviral gene transfer in cancer cells expressing various levels of coxsackievirus and adenovirus receptor.
OBJECTIVE
Loss of coxsackievirus and adenovirus receptor (CAR) is frequently observed in malignant cancer, hampering adenoviral gene therapy approaches. Complexing adenovirus with cationic liposomes can increase adenoviral transgene expression, particularly in cells with CAR-deficiency. We investigated whether other factors such as lipid composition might be involved in determining the efficiency of liposome-complexed adenoviral gene transfer in cancer cells.


METHODS
Human cancer cell lines with different expression levels of CAR were infected with a GFP transgene. The efficiency of transgene expression was assessed by determining GFP expression using FACS analysis.


RESULTS
The efficiency of liposome-complexed adenoviral gene transfer was dependent on the lipid composition constituting liposomes. Polyethylene glycol (PEG)-containing liposomes were most effective in increasing liposome-complexed adenoviral gene transfer. In CAR-deficient cells, use of PEG-containing liposomes enhanced adenoviral gene transfer, whereas in CAR-expressing cells enhancement varied depending on cell type. In some CAR-expressing cells, the effect of liposome complexing was even comparable to that in CAR-deficient cells. Increased adenoviral transgene expression following complexing with PEG-containing liposomes correlated with liposome uptake in cancer cells.


CONCLUSIONS
Liposome-complexed adenoviral gene transfer appears to depend on lipid composition and the level of liposome uptake by cancer cells, in addition to CAR levels. Our study suggest that these multiple factors should be considered in designing liposome-complexed adenoviral vectors to improve outcomes of current adenoviral cancer gene therapies.
Lee
E M
EM
Research Institute, National Cancer Center, 809 Madu-Dong, Ilsan-gu, Goyang, Gyeonggi, Korea.
Hong
S H
SH
Lee
Y J
YJ
Kang
Y H
YH
Choi
K C
KC
Choi
S H
SH
Kim
I H
IH
Lim
S J
SJ
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D002455:Cell Division; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008081:Liposomes; D008164:Luminescent Proteins / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D011092:Polyethylene Glycols / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D019076:Transgenes / Q000502:physiology; D014407:Tumor Cells, Cultured
C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D016023:Integrins; D008081:Liposomes; D008164:Luminescent Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011991:Receptors, Virus; C085301:adenovirus receptor; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols