Gene therapy with modified U1 small nuclear RNA.

INTRODUCTION: More than 15% of all disease-causing mutations result in mRNA splicing defects. U1 snRNA binds to the 5' splice site (5'ss) through base pairing. Mutation-adapted U1 snRNA (with compensatory U1 snRNA changes) and exon-specific U1 snRNA (complementary to intronic sequences) have been shown to suppress 5'ss mutations in cellular and animal models. Areas covered: The history, mechanism of action, and efficacy of U1 snRNA-mediated gene therapy are covered. The clinical utility of this technology and its limitations will be discussed. Expert commentary: Recently, gene therapies with mutation-adapted U1 snRNAs have been conducted on animal models, including aromatic l-amino acid decarboxylase deficiency and spinal muscular atrophy. However, although U1-mediated therapy has the advantage of maintaining the regulated expression of defective genes, its accuracy and efficacy needs to be improved before clinical application of this technique is possible.