Investigations of the potential use of ruthenium-ODN conjugates as antisense agents in chronic myeloid leukaemia

Abstract

The work presented in this thesis describes the synthesis of two ruthenium oligodeoxynucleotide (ODN) conjugates and their application as potential photoactive antisense agents in a model Chronic Myeloid Leukaemia (CML) system. The target 34mer ODN sequence chosen for the model system represents the messenger RNA sequence transcribed from the breakpoint region of the bcr/abl oncogene on the Philadelphia chromosome, an abnormal chromosome specific to CML cells. The overall aim of this work is augmentation of an antisense effect through site-specific photochemical targeting of the target 34mer ODN sequence thus, in theory, suppressing leukaemic mRNA expression and subsequent oncoprotein production.