Project: Variant-specific neurodevelopmental mechanisms and therapeutic target discovery in Okur-Chung Neurodevelopmental Syndrome using patient-derived iPSC models

Kyle Fink

Lead Investigator: Kyle Fink, PhD | UC Davis


Grant Details:



Project funded for one year starting in 2026 for a total of $50,000.

Aims of Grant: 


Individuals with OCNDS present with developmental delay, intellectual disability, speech impairment, autism spectrum disorder-related features, epilepsy, and behavioral challenges. However, the molecular and cellular mechanisms by which variants in the CSNK2A1 gene produce these neurological characteristics remain poorly understood, in part because no established human neuronal models exist for the disorder. Additionally, no therapeutic studies have evaluated whether correcting disease-causing variants in CSNK2A1 can restore healthy function in neurons.  


This project will address both gaps using patient-derived induced pluripotent stem cells (iPSCs), which are adult cells reprogrammed into a stem-cell state that can differentiate into nearly every cell type. The iPSCs will be differentiated into neural precursors and neurons, providing a model of human brain development in both a typical genetic background and one carrying OCNDS-causing variants. The structure and function of these neural cells will be examined to determine how CSNK2A1 variants affect neuronal development. 


After the neuronal cells have been characterized, prime editing will be used to try and correct the disease-causing CSNK2A1 variant in the patient-derived cells; the variant for this project is the most common variant seen in OCNDS, K198R. Prime editing is a precise gene-editing approach that rewrites a targeted DNA sequence without creating double-stranded breaks, which are cuts through both strands of the DNA double helix. Cells often repair such breaks imperfectly, causing unintended insertions or deletions in the DNA. Avoiding these breaks reduces the risk of unintended changes. The editing components will be delivered using an adeno-associated virus (AAV), a virus that does not cause disease and is commonly used to carry genetic material into cells. 


Successful completion of this project will clarify the mechanisms underlying the neurological dysfunction in OCNDS and determine whether prime editing can rescue that dysfunction, establishing a foundation for future therapeutic development.