Development of peritoneal tumor-targeting vector by in vivo screening with a random peptide-displaying adenovirus...

Area of Science:

• Gene Therapy
• Oncology
• Biotechnology
• Virology

Background:

• Targeting gene transfer at the cell-entry level is crucial for effective vector development.
• Previous attempts to redirect adenovirus vectors via capsid engineering showed limited success due to unknown targeting ligands.
• Cell surface receptor expression can differ significantly between in vitro cultures and in vivo tumor tissues.

Purpose of the Study:

• To overcome limitations in targeting adenovirus vectors by developing a novel screening strategy.
• To identify adenovirus vectors with enhanced infectivity for specific cancer cells in a relevant in vivo model.
• To evaluate the utility of in vivo screening for discovering targeted vectors.

Main Methods:

• Construction of a random peptide library displayed on the adenoviral fiber knob.
• In vitro screening of the peptide display-adenovirus library on cancer cell lines.
• In vivo screening of the library in a peritoneal dissemination model of AsPC-1 pancreatic cancer cells.

Main Results:

• A selected peptide (PFWSGAV) displayed on the adenovirus vector demonstrated significantly higher infectivity in AsPC-1 peritoneal tumors compared to non-targeted vectors.
• The PFWSGAV-displaying vector showed specific targeting to AsPC-1 peritoneal tumors, with no increased infectivity in other organs or tumor types.
• In vivo screening yielded a vector with superior tumor-specific infectivity compared to vectors selected through in vitro screening.

Conclusions:

• In vivo screening of peptide display-adenovirus libraries is a powerful strategy for developing targeted vectors.
• The identified PFWSGAV-displaying vector shows promise for targeted gene delivery in pancreatic cancer.
• This vector-screening system can accelerate the development of targeted adenovirus vectors for diverse medical applications.