Introduction: Marfan syndrome is one of the most common dominantly inherited connective tissue disorders, affecting 2-3 in 10,000 individuals, and is caused by one of over 1800 unique FBN1 mutations. Such mutations result in production of two different fibrillin-1 monomers that are unable to form functional microfibrils, resulting in destabilisation of the extracellular matrix. Disease management requires invasive surgical intervention and use of medications aimed at slowing disease progression, thus the need for new therapeutics. We aim to use short, synthetic nucleic acid sequences called antisense oligonucleotides to manipulate FBN1 exon selection during pre-mRNA splicing. FBN1 exon 59 harbours over 20 unique mutations, encodes one of 43 repeated motifs and its removal does not alter the reading frame. Therefore we hypothesise that removing exon 59 will allow production of identical monomers capable of forming functional microfibrils. Procedures: Antisense oligonucleotide sequences were optimised using 2ʹ-O-Methyl modified bases on a phosphorothioate backbone (2ʹOMe‑PS), transfected into healthy control and patient fibroblasts. The most effective sequence was synthesised as a phosphorodiamidate morpholino oligomer (PMO), a chemistry shown to be safe and effective clinically. Transfected cells were assessed for fibrillin-1 expression and morphology via immunofluorescent staining. Results: Exon 59 was skipped in ~45% of FBN1 transcripts in healthy cells transfected with the 2ʹOMe‑PS antisense oligonucleotides, whereas PMO‑59 induced exon 59 skipping in healthy (50%), c.7205‑2A>G (90%) and p.Arg2414X (80%) patient cells after 10 days in culture. Immunofluorescent staining revealed a corresponding increase in fibrillin-1 microfibrils when target exon skipping was greater than 75%. Conclusions: Exon 59 can be efficiently removed from FBN1 pre-mRNA in fibroblasts from two different Marfan syndrome patients, resulting in increased microfibril formation. We show proof-of-concept that removal of mutation harbouring exons from FBN1 pre-mRNA allows the production of internally truncated but identical monomers capable of forming microfibrils, potentially reducing disease severity.