Enhancement of adenoviral transduction with polycationic liposomes in vivo.

Abstract:

: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.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Lee SG,Yoon SJ,Kim CD,Kim K,Lim DS,Yeom YI,Sung MW,Heo DS,Kim NK

doi

10.1038/sj.cgt.7700237

subject

Has Abstract

pub_date

2000-10-01 00:00:00

pages

1329-35

issue

10

eissn

0929-1903

issn

1476-5500

journal_volume

7

pub_type

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