Christou, Marie-Grace2013-11-072013-11-0720042004Source: Masters Abstracts International, Volume: 43-06, page: 2235.http://hdl.handle.net/10393/26609http://dx.doi.org/10.20381/ruor-9711Hepatitis C virus (HCV) is the etiologic agent responsible for the majority of cases of non-A, non-B hepatitis. It is estimated that 2% of the world's population is infected with hepatitis C with roughly 75% of infections progressing into a chronic state. Current interferon therapy is largely ineffective against chronic Hepatitis C due to the induction of interferon-resistance by HCV. The underlying mechanisms for resistance to interferon therapy have been widely studied and documented and as is the case in interferon resistant malignancies, there is some evidence that HCV infected cells are more susceptible to infection by interferon sensitive viruses. Most current research into novel HCV therapeutics has focused on the discovery of inhibitors of viral replication. However, the high mutation rate of the HCV genome makes it a virtual certainty that viral variants resistant to protease and/or polymerase inhibitors will arise. As an alternative approach, we have designed a therapeutic strategy that exploits both the expression of a viral protease in infected cells as well as the defects in the interferon pathway to build selectively active therapeutics that target and kill HCV infected cells. Initial experiments showed some promise using this approach and indicated areas for further development. Conditionally replicating viruses failed to rescue in HCV expressing cell lines, thus requiring further modification. A separate approach involving conditional stabilization of the suicide gene HSV-1 TK was successful with a two-fold increase in the expression levels of TK in cells co-expressing HCV protease.102 p.enChemistry, Biochemistry.Chemistry, Pharmaceutical.Health Sciences, Pharmacy.Thesis