Enhancement of adenoviral transduction with polycationic liposomes in vivo.
Although the high transfection efficiency with adenovirus in vitro is well documented, it is still not clear whether adenoviral vectors are effective in vivo in solid tumor models. In our preliminary experiment, transduction of tumor tissue was limited to just around the injection site after intratumoral injection of the adenoviral vector. To improve the transduction efficiency in vivo, we tried a combination of adenoviral vector and liposome in our animal model. Adenovirus carrying human placental alkaline phosphatase (AdALP) and Lipofectamine or 1,3-di-oleoyloxy-2-(6-carboxyspermyl)-propylamide were used as a marker gene and the cationic liposome, respectively. A >15-fold increase in the transfection efficiency was observed in CT26 tumor cell lines with the combination of AdALP adenovirus carrying murine granulocyte-macrophage colony-stimulating factor (AdmGM-CSF), and liposome compared with adenovirus alone, showing the feasibility of the combination treatment. In the animal model, with the combination of liposome and AdALP, deeper and wider distribution of the marker gene in the tumor mass was shown. We conclude that the limitations of direct application of adenoviral vectors in a solid tumor model could be overcome by the use of cationic liposomes. This approach will facilitate the more effective delivery of adenoviral vectors in a clinical trial setting.
Lee
S G
SG
Cancer Research Center, Department of Internal Medicine, College of Medicine, Seoul National University, Korea.
Yoon
S J
SJ
Kim
C D
CD
Kim
K
K
Lim
D S
DS
Yeom
Y I
YI
Sung
M W
MW
Heo
D S
DS
Kim
N K
NK
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D000256:Adenoviridae / Q000235:genetics*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D003131:Combined Modality Therapy; D017931:DNA Primers / Q000737:chemistry; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic / Q000379:methods*; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D008081:Liposomes; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000469:Alkaline Phosphatase