Exploring the SINEUP properties as RNA therapeutic tools in ARX polyalanine models for West syndrome.

ARX (Aristaless-related homeobox gene), is a crucial gene for development of interneuron in the fetal brain, implicated in intellectual disability associated with a severe form of Epilepsy. It is caracterized by a trinucleotide (GCN) repeats with high tendency to expand causing the alanine elongations (polyA). We report here an innovative long non-coding RNA-based technology, the application of the SINEUP-strategy, to correct ARX deficiency. These method is able to enhance protein translation by using synthetic long non coding RNA (lncRNA). SINEUPs are a new class of RNA therapeutics that allows to design gene-specific approaches to treat, malignant epilepsy diseases and many other neuropathologies with seizure linked to insufficient activity of chromatin and/or transcriptional regulators.