Background. Aberrant splicing represents a common disease-causing mechanism in CF and exon skipping is one of the most frequent defect. We recently reported that modified U1 core spliceosomal components (named ExSpe U1) , when specifically engineered to bind in the intron downstream the 5'ss rescues splicing of defective exons. This therapeutic activity can be observed in CFTR exon 13 and 5, where the modified U1s efficiently correct different splicing defects present either at the 5'ss or at the exonic splicing regulatory elements.
Hypothesis. The molecular mechanism of ExSpeu1 -mediated splicing enhancement and effect in vivo are largely unknown.