We work on improving the delivery of ASO into cells in adult tissues, enabling the therapeutic use of ASO for treatment of a broad range of diseases. Chemical structures have been found that, when linked to a PMO, enhance the delivery of the PMO from blood into the cytosol of cells. Dr. Moulton invented a class of compounds, the peptide-conjugated Morpholino oligos (PPMO), which are in clinical trials and are the workhorse molecules produced in my laboratory for many applications for eukaryotic and prokaryotic systems.
Our current understanding of PPMO’s mechanism of action is shown in the upper left figure. PPMO have been investigated for many applications as illustrated in the upper right figure. Our team is actively researching on alternative strategies for enhancing Morpholino delivery in vivo by other forms of chemical modifications, formulations and tissue-specific targeting. Recently, our lab has developed formulations that can significantly enhance the specific activity of a range of ASO types including PMO, PPMO, 2’OMe PS, 2’MOE PS, and gapmer ASO.