In this research project the structural and biophysical properties of morpholinos, a class of
nucleic acid therapeutics approved for treating Duchenne muscular dystrophy, a severe
genetic disorder, are investigated. Despite their therapeutic importance, little is known
about their high-resolution 3D structure or how they interact with DNA and RNA. This
project aims to address these gaps by synthesizing specialized morpholino building blocks,
optimizing their production, and using advanced techniques like X-ray crystallography and
NMR spectroscopy to study their structure and dynamics.
The research seeks to answer critical questions, such as how morpholinos bind to DNA/RNA,
how they influence hybrid structures, and whether their behavior mirrors that of natural
DNA/RNA. By uncovering these details, the team hopes to improve the design and
effectiveness of morpholino-based therapies. This innovative work not only advances our
understanding of morpholinos but also sets a new benchmark in the field of nucleic acid
structural biology, with potential implications for the development of future therapeutics.