Production of CHM R293X cell model system to study the rescue of the Rab Escort Protein-1 expression by TRIDs nonsense suppression activity

Abstract

Choroideremia is an inherited genetic disorder caused by several mutations in the CHM gene, which codifies for Rep1 protein strictly linked in intravesicular trafficking. The Rep1 lack causes choroid and photoreceptors degeneration, leading firstly to night blindness and at last to complete blindness. About 39% of mutations on the CHM gene are represented by nonsense mutations, which insert a premature termination codon in the reading frame of respective mRNA, with the production of truncated non-functional protein. Nowadays there is no cure for diseases caused by nonsense mutations, but a promising approach is the suppression therapy using TRIDs molecules (translational readthrough-inducing drugs). In our study, a CHMR293X/R293X cell model system was produced to evaluate the activity of three new optimized molecules (NV848, NV914, and NV930) in the rescue of the Rab-Escort-Protein-1 (Rep1) expression.