This project aims to develop a first-of-its-kind treatment for Bohring-Opitz Syndrome (BOS), a rare and severe brain disorder in children caused by mutations in the ASXL1 gene. By removing the harmful products of the mutant gene, we hope to improve neuronal functions and behaviors in the brain.
2026 Tullie and Rickey Families Spark Awards finalist
Zhen Dong, Ph.D.
Can we silence a toxic gene to treat a rare and severe brain disorder in children?
Children with Bohring-Opitz Syndrome (BOS) face severe challenges, including seizures, learning difficulties, trouble eating, poor growth, and increased cancer risk. There’s currently no cure for this rare genetic condition.
BOS results from pathogenic ASXL1 gene variants that produce toxic proteins, disrupting cellular chromatin structure and interfering with gene regulation during development. ASXL1 is crucial for both brain and bone marrow development.
Our project proposes using antisense oligonucleotides (ASOs)—short synthetic genetic sequences that act as tiny “molecular scissors” that can eliminate faulty genetic instructions before they result in harmful protein production. ASOs have already proven successful in treating other rare genetic diseases like spinal muscular atrophy and Duchenne muscular dystrophy.
We will create engineered human induced pluripotent stem cells with BOS-associated ASXL1 variants, differentiate them into neurons, and test ASO treatments to identify those that reduce harmful proteins while preserving healthy ones.
This work could yield the first targeted BOS therapy and advance treatments for related disorders and other rare brain diseases.
“My project explores novel molecular mechanisms and therapeutic strategies that have not been well studied. This support gives me the freedom to test out bold ideas early on, and have a chance to collect the preliminary data for larger grants.”
