Can an Antisense Oligonucleotide Exon Skipping Rewrite the Story of N-Acetylglucosamine-1-Phosphotransferase Deficiency?

Mucolipidosis II (ML II) is a Lysosomal Storage Disorder caused by N-acetylglucosamine-1-phosphotransferase (GlcNAc-PT) deficiency, which impairs the trafficking of lysosomal hydrolases. Of all ML II mutations, c.3503_3504delTC in GNPTAB exon 19 is the most frequent, making it a good target for a personalized therapy. Here, we explored an innovative therapeutic strategy based on the use of antisense oligonucleotides (ASOs). Previously, in ML II patients’ fibroblasts, we tested ASOs to induce exon 19 skipping in pre-mRNA, successfully generating an in-frame mRNA (Matos et al., 2020). Now, our aim is to determine whether this in-frame transcript leads to increased GlcNAc-PT levels improving ML II cellular phenotype.

Palavras-chave

Mucolipidosis II Antisense Oligonucleotides Lysosomal Storage Diseases Genética Humana Doenças Genéticas Terapias de RNA Doenças Lisossomais de Sobrecarga Mucolipidose tipo II GNPTAB Gene RNA Therapy

URI

http://hdl.handle.net/10400.18/11067

Projetos de investigação

Innovative & personalized RNA-based therapies for rare diseases and development of models for their testing: application to Mucolipidosis II

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Coleções

DGH - Apresentações orais em encontros nacionais

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Sem licença CC

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