Antisense Oligonucleotide Therapy to Correct CFTR Function in People with Cystic Fibrosis

Cystic fibrosis (CF) is the most common life-threatening recessively inherited disease in Caucasians that has no cure. Novel therapeutics such as antisense oligonucleotides (AOs) have potential to be personalised treatments for people with CF. This thesis investigated 8 CFTR exons whose splicing could be altered with AOs. It was proposed that exon skipping to restore the CFTR reading frame could improve CFTR protein production for selected disease-causing mutations and reduce disease severity. Assessments were conducted in human primary airway epithelial cells, with lead AO sequences identified. Future work will investigate the functional capacity of the internally truncated CFTR protein.