Science Director Charles River, England, United Kingdom
The emergence of splicing modulation with anti-sense oligonucleotides (ASO) and more recently small molecules, has opened up many opportunities to target gene products that were previously thought to be undruggable. Furthermore, small molecule splicing modulators for neurodegenerative diseases provide the potential advantages of greater distribution, non-invasive delivery methods and higher patient accessibility compared to ASOs. The development of small molecules that modulate the splicing process of primary RNA is discussed with examples from SMN2 splicing modulators for spinal muscular atrophy (SMA) and huntingtin (Htt) splicing modulators for Huntington's disease. In particular, the origins of the chemical starting points and screening cascade will be presented.
