This project will develop strategies to mask biological surfaces with polymer coats, effectively cloaking them from unwanted interactions with the immune system. This can be a very powerful way to improve the biocompatibility of therapeutic viruses and cells, creating hybrid nano and micro structures. It is also safe, as the coat is not inherited and it is diluted out when the virus or cell divides. Although we have already developed simple surface-coating strategies, masking efficiency is limited by incomplete coverage (reflecting steric hindrance for additional polymers to gain access to partially-coated surfaces). Accordingly, in this project, we are developing a system to initiate polymerization actually on the biological surface, promoting growth of the polymer away from the surface and improving the overall coating efficiency. We also aim to cause dendrimeric branching of the growing polymer, a technique that should increase the footprint of coverage by each unit, minimizing the number of points of attachment required. This technology will be used immediately for development of a virotherapy treatment for metastatic cancer, based on adenoviruses that can replicate selectively in cancer cells and kill them. At present, this powerful approach is limited by the difficulty of delivering the virus intravenously, since the human bloodstream contains many anti-virus antibodies, however this 'starburst' cloaking approach will enable intravenous delivery and thereby permit the therapeutic virus to gain access to widespread cancer deposits, and destroy them by lytic infection. This project will develop a nanostructured cloaking strategy for biological surfaces, exemplified in the field of cancer virotherapy, and hence the immediate health beneficiaries will be patients with metastatic cancer. This platform strategy applies to modification of viruses but also can be utilized for non-genetic cloaking of other complex nanostructures for drug delivery or cells for xenotransplantation. The technology should therefore find important applications in new treatments of acquired (e.g. hepatitis) and inherited diseases (e.g. cystic fibrosis) and notably in development of antibody-resistant viral vaccines suitable for repeated use in diseases such as HIV, malaria, TB and influenza. ? ? ?
