An engineered U1 snRNA-based therapeutic approach can efficiently rescue a 5’ splice site mutation causing Mucolipidosis type III

A 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.

Palavras-chave

Genética Humana Doenças Genéticas Terapias de RNA Doenças Lisossomais de Sobrecarga Mucilipidose tipo III Terapias com U1 snRNA modificados Lysosomal Storage Disorder Mucolipidosis III 5’ Splice-Site Mutation U1 snRNA-Based Therapy ExSpeU1

URI

http://hdl.handle.net/10400.18/11066

Coleções

DGH - Apresentações orais em encontros nacionais

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Sem licença CC

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