Poster #: 102
Lentiviral delivery of epigenetic therapies in RTT patient brain organoids
Mentor: Klaudia Braczyk, PhD
Rett syndrome (RTT) is a rare neurodevelopmental disease caused by mutations in the MECP2 gene located on the X chromosome, leading to severe motor and cognitive impairments in patients. Currently, there is no cure for RTT and there is a strong need for novel therapeutic approaches and patient-relevant models of RTT. In heterozygous female patients, there is a potential for functional rescue through CRISPR-based reactivation of the inactive healthy copy of this gene. Traditional, two-dimensional neuronal cultures present many challenges in modeling complex microenvironments of the brain, and three-dimensional brain organoids have recently emerged as a highly patient-relevant model. In this study, lentiviral delivery of a potential CRISPR-based therapeutic into RTT patient-derived brain organoids was investigated. Results show effective plasmid expression in bacteria, delivery to the packaging platform, and early indications of organoid transduction, paving the path for future studies on epigenetic reactivation of MECP2 in the brain-relevant model.