Date of Award
6-3-2024
Degree Type
Thesis
Degree Name
Master of Science (MS)
Department
Neuroscience
First Advisor
Rocco Gogliotti
Abstract
Rett Syndrome (RTT) is a neurodevelopmental disorder that is characterized by a myriad of debilitating symptoms impacting nearly every aspect of life, including motor and gait impairment, social and cognitive deficits, as well as seizures and breathing abnormalities. RTT is caused by X-linked de novo loss-of-function mutations in the methyl-CpG binding protein 2 gene (MECP2), which is an essential epigenetic modulator. Any cure for RTT must directly target MECP2, a highly dosage-sensitive gene. This thesis developed a novel MECP2-targeted therapeutic approach using site-blocking antisense oligonucleotides to prevent microRNA-induced repression of MECP2, allowing fine-tuned control of gene expression. Here we report positive results of a novel sbASO that has efficacy across common RTT-pathogenic mutations and whose target microRNA levels are not impacted by disease state. The strategy described herein could provide a cure for RTT that is safer and more personalized to each patient compared to potential gene therapies.
Recommended Citation
Rhee, Yewon, "Fine-Tuning Gene Expression: A Novel Therapeutic Approach for Rett Syndrome" (2024). Master's Theses. 4520.
https://ecommons.luc.edu/luc_theses/4520
