As proof of principle, we validated the treatment effect on splicing for several disease-causing mutations using patient cell lines or minigenes, and demonstrate the potential therapeutic feasibility of targeting splicing in patients with cystic fibrosis (CFTR), cholesterol ester storage disease (LIPA), Lynch syndrome (MLH1), and familial frontotemporal dementia (MAPT). Here, CFTR is linked to cholesteryl ester storage disease.