This project aims to develop an aptamer-based technology to enhance the in-vivo survival of oncolytic viruses and thus the efficiency of virotherapy. Oncolytic viruses (OVs) can selectively replicate in tumor cells, leading to lysis of the tumor. OVs are particularly effective against metastatic cancers, which are especially difficult to treat conventionally. However, OVs can be deactivated by antiviral neutralizing antibodies (nAbs) and cleared from the circulation. In this project we plan to use virus binding aptamers to modify the surface of OVs via Apta-ViSh technology, in order prevent their recognition by nAbs. Furthermore, we are planning to shield the nAbs via Apta-AntiviSh technology, using different aptamers, to enhance the anticancer activity of OVs by a dual mechanism. This research project will allow biopharmaceutical companies to engineer new aptamer-based anticancer drugs. This project will make cancer treatment more efficient and will alleviate the burden of cancer on the national economy.