Engineered tRNAs efficiently suppress CDKL5 premature termination codons.

ABSTRACT: The CDKL5 deficiency disorder (CDD) is a severe neurodevelopmental disorder characterized by early-onset epilepsy, intellectual disability, motor and visual dysfunctions. The causative gene is CDKL5, which codes for a kinase required for brain development. There is no cure for CDD patients; treatments are symptomatic and focus mainly on seizure control. Several pathogenic variants are loss-of-function, but recent studies suggest that the CDD phenotype is sensitive to the CDKL5 gene dosage. Therefore, mRNA-targeted correction strategies that respect the physiological regulation of CDKL5 could be a valid alternative to augmentative gene therapy. Nonsense mutations cause ~ 11% of CDD cases, and these patients might benefit from readthrough therapies. We proved that drug-mediated readthrough e

SUBMITTER: Pezzini S 

PROVIDER: S-EPMC11685654 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature