Development of Engineered-U1 snRNA Therapies: Current Status

Gonçalves, Mariana; Santos, Juliana Inês; Coutinho, Maria Francisca; Matos, Liliana; Alves, Sandra

http://hdl.handle.net/10400.18/9126

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Authors

Gonçalves, Mariana

Santos, Juliana Inês

Coutinho, Maria Francisca

Matos, Liliana

Alves, Sandra

Abstract(s)

Splicing of pre-mRNA is a crucial regulatory stage in the pathway of gene expression. The majority of human genes that encode proteins undergo alternative pre-mRNA splicing and mutations that affect splicing are more prevalent than previously thought. Targeting aberrant RNA(s) may thus provide an opportunity to correct faulty splicing and potentially treat numerous genetic disorders. To that purpose, the use of engineered U1 snRNA (either modified U1 snRNAs or exon-specific U1s-ExSpeU1s) has been applied as a potentially therapeutic strategy to correct splicing mutations, particularly those affecting the 5' splice-site (5'ss). Here we review and summarize a vast panoply of studies that used either modified U1 snRNAs or ExSpeU1s to mediate gene therapeutic correction of splicing defects underlying a considerable number of genetic diseases. We also focus on the pre-clinical validation of these therapeutic approaches both in vitro and in vivo, and summarize the main obstacles that need to be overcome to allow for their successful translation to clinic practice in the future.

Description

Review
(This article belongs to the Special Issue Future Challenges and Trends of Nucleic Acids)

Keywords

U1 snRNA (Small Nuclear RNA)-based Therapies Modified U1 snRNAs Exon-specific U1 snRNAs (ExSpeU1s) 5′ splice-site (5′ss) Splicing Mutations Splicing Correction Genética Humana Doenças Genéticas