文档介绍：Development of Peritoneal Tumor-Targeting Vector by In
Vivo Screening with a Random Peptide-Displaying
Adenovirus Library
. .
Takeshi Nishimoto1,3 , Yuki Yamamoto1 , Kimiko Yoshida1, Naoko Goto1, Shumpei Ohnami2,
Kazunori Aoki1*
1 Division of Gene and Immune Medicine, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan, 2 Central Radioisotope Division, National Cancer Center
Research Institute, Chuo-ku, Tokyo, Japan, 3 Department of Neurosurgery, Graduate School of Medicine, Hiroshima University, Minami-ku, Hiroshima, Japan
Abstract
The targeting of gene transfer at the cell-entry level is one of the most attractive challenges in vector development.
However, attempts to redirect adenovirus vectors to alternative receptors by engineering the capsid-coding region have
shown limited ess, because the proper targeting ligands on the cells of interest are generally unknown. To e
this limitation, we have constructed a random peptide library displayed on the adenoviral fiber knob, and have essfully
selected targeted vectors by screening the library on cancer cell lines in vitro. The infection of targeted vectors was
considered to be mediated by specific receptors on target cells. However, the expression levels and kinds of cell surface
receptors may be substantially different between in vitro culture and in vivo tumor tissue. Here, we screened the peptide
display-adenovirus library in the peritoneal dissemination model of AsPC-1 pancreatic cancer cells. The vector displaying
a selected peptide (PFWSGAV) showed higher infectivity in the AsPC-1 peritoneal tumors but not ans and other
peritoneal tumors pared with a non-targeted vector. Furthermore, the infectivity of the PFWSGAV-displaying vector
for AsPC-1 peritoneal tumors was significantly higher than that of a vector displaying a peptide selected by in vitro
screening, indicating the usefulness of in vivo screening in exploring the targeting vectors. This vector-screening syst