Researcher ORCID Identifier
0009-0009-6344-602X
Graduation Year
2025
Document Type
Campus Only Senior Thesis
Degree Name
Bachelor of Arts
Department
Biochemistry
Reader 1
Barbara Bailus
Reader 2
Kyle Jay
Terms of Use & License Information
Rights Information
2025 Rachel E Stoub
Abstract
Angelman Syndrome (AS) is a rare neurodevelopmental disorder caused by mutations in the UBE3A gene, resulting in a lack of UBE3A protein within neuronal cells due to the silencing of the paternal UBE3A gene. This leads to severe neurological symptoms, including developmental delays, motor dysfunction, and seizures, sadly with no current cure. Enzyme replacement therapy (ERT) has shown promise in treating disorders caused by protein depletion; however, its application to AS is hindered due to the inability of UBE3A to cross the blood-brain barrier (BBB). This study explores the potential of a novel cell-penetrating peptide (CPP), ZIP, derived from a neuronal virus, to deliver UBE3A across the BBB.
Z-UBE3A proteins were designed and purified, and their cellular uptake and stability were assessed in neuroblastoma cells. Collectively, the data supports the use of the Z-UBE3A purified from baculovirus as a potential therapeutic candidate for enzyme replacement therapy within AS. It achieves high full-length protein purity and effective cell penetration, and the cellular degradation pathways can act on it, preventing accumulation within the brain. The ZIP peptide appears crucial for cell penetration, highlighting its importance within ERT.
Ongoing experiments are being conducted, evaluating Z-UBE3A’s effects on human brain organoids and testing intravenous administration in mice. The ultimate aim of this work is to establish Z-UBE3A as a viable intravenous enzyme replacement therapy for AS. Additionally, the application of cell-penetrating peptides like ZIP offers broader potential in developing ERTs capable of bypassing the BBB, which could aid in advancements across the neurological therapeutic fields.
Recommended Citation
Stoub, Rachel; Bailus, Barbara Dr.; and Correa, Delihla, "UBE3A Enzyme Replacement Therapy for Angelman Syndrome" (2025). Scripps Senior Theses. 2502.
https://scholarship.claremont.edu/scripps_theses/2502
This thesis is restricted to the Claremont Colleges current faculty, students, and staff.
