Related Experiment Video
Updated: May 18, 2026
Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
Infectivity-selective oncolytic adenovirus developed by high-throughput screening of adenovirus-formatted library
Yoshiaki Miura1, Satoshi Yamasaki, Julia Davydova
1Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Abstract:
Adenovirus (Ad) is a potent gene-delivery vehicle and has frequently been used for designing oncolytic viruses. However, lack of selectivity on infection has hampered the achievement of sufficient in vivo efficiency. Here, we developed a novel oncolytic virus system, infectivity-selective oncolytic adenovirus (ISOAd), via direct high-throughput screening of a high-diversity targeting-ligand library in adenoviral format. Through our newly designed rescue virus system, the high-diversity Ad library carrying the random seven amino acid sequences ligand-library in the AB-loop of its fiber-knob region (5 × 10(9) diversity) was successfully generated. During the screening of this library with the cells expressing the target molecule (mesothelin, MSLN), the AB-loop sequence of the virus clones converged to one dominant sequence and a novel MSLN-targeting sequence was isolated. The virus with the isolated motif showed selective infectivity to MSLN-positive cells in vitro. In vivo, it exhibited a selective and potent antitumor effect resulted from the viral replication in MSLN-positive xenografts. The ISOAd is a novel class of oncolytic Ad, which has selectivity at the step of transduction. The selectivity at the stage of infection can open new perspectives in oncolytic Ad therapy for various diseases.
Insights
Researchers developed a novel infectivity-selective oncolytic adenovirus (ISOAd) by screening a large ligand library. This engineered virus specifically targets mesothelin-positive cancer cells, enhancing antitumor effects and offering new therapeutic possibilities.
Area of Science:
- Oncolytic virotherapy
- Gene therapy
- Molecular targeting
Background:
- Adenoviruses (Ad) are effective gene-delivery vehicles for oncolytic virotherapy.
- Limited tumor selectivity of conventional adenoviruses hinders in vivo efficacy.
- Targeting specific molecules on cancer cells can improve oncolytic virus performance.
Purpose of the Study:
- To develop a novel oncolytic adenovirus with enhanced infectivity selectivity.
- To isolate a specific targeting ligand for mesothelin (MSLN) using high-throughput screening.
- To evaluate the in vitro and in vivo efficacy of the engineered oncolytic adenovirus.
Main Methods:
- Generation of a high-diversity adenovirus library with random ligand sequences in the fiber-knob AB-loop.
- High-throughput screening of the library against mesothelin-expressing cells.
- Isolation and characterization of a novel MSLN-targeting ligand.
- In vitro and in vivo evaluation of the infectivity-selective oncolytic adenovirus (ISOAd).
Main Results:
- A dominant MSLN-targeting sequence was identified from the screened library.
- The engineered ISOAd demonstrated selective infectivity towards MSLN-positive cells in vitro.
- ISOAd exhibited potent and selective antitumor effects in MSLN-positive xenografts in vivo.
- The virus achieved selectivity at the transduction stage.
Conclusions:
- ISOAd represents a new class of oncolytic adenovirus with infection-stage selectivity.
- Targeted infection capability enhances the therapeutic potential of oncolytic adenoviruses.
- This approach offers new perspectives for treating various diseases using oncolytic adenovirus therapy.
