Duchenne Muscular Dystrophy. The cloning of the Duchenne muscular dystrophy (DMD;dystrophin) gene has led to effective prenatal screening for families with a history of the disease. However, no effective treatment is available and gene replacement is currently the only therapeutic option. The unusually large size of the DMD gene presents special problems for the design of effective minigenes. In recent years our research efforts have been directed toward a) identifying and characterizing important muscle-specific transcriptional domains within the human DMD gene; b) analysis of dystrophin protein function at the early stages of myogenesis; and c) assessing the potential for adenovirus-mediated gene transfer to DMD patient myoblasts. New knowledge in these areas will be applied to the design of therapeutically-effective DMD minigenes and the development of a safe and effective gene delivery system.
Breast cancer. Programmed cell death (apoptosis) signalling pathways have >been recognized as an important component of multistep carcinogenesis and this knowledge has led to new cancer treatment strategies based on cell death induction. Studies in our laboratory of the cytotoxic effects on human breast cancer cells of recombinant p53 overexpression and herpes simplex virus thymidine kinase/gancyclovir treatment have affirmed the need for a better understanding of the molecular pathways that signal apoptosis. Current >research efforts are directed toward elucidating the molecular basis for the increased resistance of tumour cells expressing wild-type p53 to these treatment strategies. Our goal is to apply this knowledge to the design of novel molecular interventions that complement conventional treatment strategies.
Gene delivery. A major obstacle to the realization of the enormous potential of gene therapy is the unavailability of a gene transfer vehicle that is safe, can be targeted to specific cell types, and provides therapeutic levels of transgene expression. Studies in our laboratory have shown that adenoviral vectors can be used to transduce DMD patient myoblasts and human breast cancer cells with high efficiency. We are currently exploring the potential of transcriptional and receptor-mediated targeting strategies applied to the adenoviral vector system in relation to DMD and the breast cancer problem.
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