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A high sensitivity assay of UBE3A ubiquitin ligase activity from Dr. Albert Keung’s Lab

The recent publication titled “A High Sensitivity Assay of UBE3A Ubiquitin Ligase Activity” from Dr. Albert Keung’s lab presents an important tool for advancing research and therapies targeting Angelman syndrome (AS) and possibly other autism spectrum disorders (ASDs). Funded by FAST, this assay (tool) provides a way to measure how effectively UBE3A protein is functioning in brain cells. Existing methods, like Western Blotting, are slow and complex, making them less suitable for large-scale testing or therapeutic development. This new assay, however, is fast, sensitive, and cost-effective, and it can detect even very small amounts of UBE3A protein. This capability makes it especially useful for potentially measuring UBE3A levels in blood or cerebrospinal fluid (CSF). Additionally, the assay can be completed in just one hour using standard lab equipment, making it a significant improvement for monitoring therapies in clinical trials or measuring biomarkers in patient samples. 

Another important feature of the assay is its ability to distinguish between normal UBE3A and mutant versions of the protein. AS can be caused by mutations in UBE3A, so being able to differentiate between the typical and mutant forms of the UBE3A enzyme is crucial for assessing the effectiveness of potential therapies. The assay is also versatile, working with various sources of UBE3A, including natural sources from the paternal UBE3A gene or engineered versions used in enzyme or gene replacement therapies. This versatility is especially valuable in early-stage research, where determining the appropriate therapeutic dose and duration of a specific therapy is essential. 

The publication of the assay in a peer-reviewed journal means that the assay can be used by any researchers interested in UBE3A, which will lead to additional improvements in sensitivity and quality. As the assay is refined, it holds the potential to further advance our understanding of UBE3A’s role in biological systems and continue to support the development of treatments for disorders related to UBE3A dysfunction.   

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