Grant: Strategic Projects - Group

One of the challenging tasks of anticancer therapy is the design of drugs eliminating only tumor cells not normal cells. Novel, targeted approaches such as gene therapy hold promise for the advanced treatment of various tumors. Among the most promising cancer gene therapy approaches are oncolytic viruses, which are able to infect, replicate in and lyse tumor cells. Recent data from clinical trials with these viruses have shown that they are safe. However, antitumor efficacy needs to be improved to make oncolytic viruses a viable treatment for cancer patients. Efficient delivery of viruses to tumor sites remains a challenge. The presence of antiviral neutralizing antibodies can pose a major obstacle to systemic virotherapy as repeat dosing is required to achieve significant therapeutic gains. In this project we plan to develop an aptamer-based technology to enhance in vivo survival of oncolytic viruses and efficiency of the anticancer treatment. The technology is called Aptamer-Facilitated Virus Protection (AptaVIP). It uses virus binding aptamers to modify the surface of two oncolytic viruses (vaccinia and vesicular stomatitis virus) in order to shield them from antibody recognition. Modification of the virus surface by non-immunogenic aptamers is an effective way of changing viral interaction with an immune system. Aptamers are single-stranded DNA oligonucleotides that can bind to a variety of different targets ranging from small molecules to proteins with high affinity and specificity. Aptamers are ligands with big potential to change the field of biomaterials. They are thermostable and can be chemically synthesized for lower price, have better batch-to-batch reproducibility, and have the simplicity of chemical modifications and tunable affinity. In addition to the improvement of oncolytic virus's systematic delivery, antiviral aptamers will be used for the affinity purification of the viruses during a manufacturing process and for aptamer-mediated virus assay (AptaVASS) as point-of-care tests in clinical applications.