Compositions and methods for treating cystic fibrosis

A method for treating cystic fibrosis (CF) in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of at least one synthetic antisense oligonucleotide (ASO) that targets a CF-conferring mutation located in exon 24 of the cystic fibrosis transmembrane conductance regulator (CFTR) pre-mRNA, thereby treating CF in the subject.

A composition comprising an ASO that induces splicing activity of exon 24 of CFTR pre-mRNA comprising 14 to 25 bases or 17 to 22 bases and having at least 80% complementarity to said CFTR pre-mRNA.

The composition of claim 62, wherein said ASO comprises 4 to 18 nucleotides upstream to said cytosine.

A kit comprising at least one ASO that targets a CF-conferring mutation located in exon 24 of CFTR pre-mRNA and:

• a. at least one CFTR modifier comprising CFTR potentiator, CFTR corrector, Translational Read-Through agent, and CFTR amplifier;
• or
• b. at least one CF drug comprising an antibiotic drug, a bronchodilator, a corticosteroid, or any combination thereof.

The kit of claim 68, wherein said at least one ASO comprises a sequence selected from the group consisting of SEQ ID Nos.:

• 4-14.

A method for producing a compound suitable for treating CF, the method comprising:

• obtaining a compound that binds to exon 24 of the CFTR pre-mRNA, assaying the skipping of exon 24 of the CFTR pre-mRNA in the presence of said obtained compound, and selecting at least one compound that induces the exclusion of exon 24 from said CFTR pre-mRNA, thereby producing a compound suitable for treating CF.