Therapeutic strategies based on modified U1 snRNAs and chaperones for Sanfilippo C splicing mutations.

ABSTRACT:

Background

Mutations affecting RNA splicing represent more than 20% of the mutant alleles in Sanfilippo syndrome type C, a rare lysosomal storage disorder that causes severe neurodegeneration. Many of these mutations are localized in the conserved donor or acceptor splice sites, while few are found in the nearby nucleotides.

Methods

In this study we tested several therapeutic approaches specifically designed for different splicing mutations depending on how the mutations affect mRNA processing. For three mutations that affect the donor site (c.234 + 1G > A, c.633 + 1G > A and c.1542 + 4dupA), different modified U1 snRNAs recognizing the mutated donor sites, have been developed in an attempt to rescue the normal splicing process. For another mutation that affects an acceptor

SUBMITTER: Matos L 

PROVIDER: S-EPMC4279800 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature