Application of synthethic long non-coding RNAs to increase synthesis of Lysine (K)-specific demethylase 5C (KDM5C) in primary mouse neurons.

Impaired chromatin regulation has a critical role in the pathophysiology of several forms of Intellectual Disability (ID) with epilepsy in infancy and childhood. Lysine (K)-specific demethylase 5C (KDM5C) is an epigenetic regulator that removes di- and tri-methyl groups of lysine 4 on histone H3 (H3K4) from transcriptional targets and is essential for neuronal survival and dendritic growth. Mutations in KDM5C gene, located at Xp11.22, are an important cause of syndromic and non-syndromic XLID in males. Moreover, changes in KDM5C expression have been implicated in the pathology of ARX-related ID, Huntington's disease and drug addiction. Here we report on the application of an innovative long non-coding RNA-based technology named SINEUP for the role of Short Interspersed Nuclear Element B2 (SINEB2) to UP-regulate translation. The application of this innovative RNA-based therapy could open a new dimension to the field of nucleic acid based therapeutics for neurological "orphan" diseases with comorbid phenotypes.