A sensitive assay system to test antisense oligonucleotides for splice suppression therapy in the mouse liver

Gallego-Villar, Lorena; Viecelli, Hiu Man; Pérez, Belén; Harding, Cary O; Ugarte, Magdalena; Thöny, Beat; Desviat, Lourdes R

doi:10.1038/mtna.2014.44

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Gallego-Villar, L., Viecelli, H. M., Pérez, B., Harding, C. O., Ugarte, M., Thöny, B., & Desviat, L. R. (2014). A sensitive assay system to test antisense oligonucleotides for splice suppression therapy in the mouse liver. Molecular Therapy : Nucleic Acids, 3, e193. https://doi.org/10.1038/mtna.2014.44

Abstract

We have previously demonstrated the efficacy of antisense therapy for splicing defects in cellular models of metabolic diseases, suppressing the use of cryptic splice sites or pseudoexon insertions. To date, no animal models with these defects are available. Here, we propose exon skipping of the phenylalanine hydroxylase (Pah) gene expressed in liver and kidney to generate systemic hyperphenylalaninemia in mice as a sensitive in vivo assay to test splice suppression. Systemic elevation of blood L-Phe can be quantified using tandem MS/