Peretto, L.Gonçalves, M.Santos, J.I.Duarte, A.J.Moreira, L.Encarnação, M.Coutinho, M.F.Pinotti, M.Balestra, D.Alves, S.Matos, L.2026-03-032026-03-032025-11-28http://hdl.handle.net/10400.18/11066A significant number of splicing mutations have been identified in Lysosomal Storage Disorders (LSDs). Mucolipidosis III (ML III) is a LSD caused by GlcNAc-1-phosphotransferase deficiency, which impairs the trafficking of lysosomal hydrolases. 10% of the genetic defects in ML III are splicing mutations, and around 45% affect 5' splice-sites (ss) thus constituting a good target for mutation specific therapies. The use of engineered U1 snRNA (either modified U1 snRNAs or exon-specific U1s - ExSpeU1s) has been applied as a potential therapeutic strategy to correct 5’ss defects. Here we used engineered U1 snRNAs to correct the GNPTAB exon 17 skipping caused by the 5’ss mutation (c.3335+6T>G) found in a ML III patient.engGenética HumanaDoenças GenéticasTerapias de RNADoenças Lisossomais de SobrecargaMucilipidose tipo IIITerapias com U1 snRNA modificadosLysosomal Storage DisorderMucolipidosis III5’ Splice-Site MutationU1 snRNA-Based TherapyExSpeU1conference object