FAST is excited to announce that we are sponsoring Dr. Albert Keung and his team at North Carolina State University to enable the preemptive generation of Angelman syndrome neuronal cell lines and organoids to accelerate drug discovery in Angelman syndrome. FAST funded the development of a biorepository for all genotypes of Angelman syndrome at Yale University, including the large deletion, mutation (missense and nonsense), ICD, UPD, and mosaic. These cell lines created through this biorepository are valuable for researchers looking to test specific disease-modifying, gene editing, or gene replacement therapies for Angelman syndrome. These patient cell lines are highly sought after by academics and industry sponsors and were developed from a simple blood sample. These lines are now being used to test different therapies for numerous pharmaceutical and biotechnology companies. Doing this work is complex, time-consuming, and requires an incredible skillset to understand how to measure UBE3A activation or expression in different parts of the neuron and know how that translates into improved cell function. FAST has created a special service, through Dr. Keung’s leadership, at NCSU, which can do this type of testing for anyone who needs it to avoid companies having to set up these lines in their own brick-and-mortar facilities. This addition to our capabilities as a community is saving months of work to get to lead candidates for the next steps in drug development. This is a great example of how FAST is accelerating the drug development lifecycle for all sponsors (academic and pharmaceutical companies) to support their work for Angelman syndrome.
The goal of this program is to create a stable infrastructure for rapidly testing potential therapeutics in human neuronal cell models of Angelman syndrome (AS). Stable, long-term support for this infrastructure will be beneficial to our community for three primary reasons:
The Keung lab is capable of applying multiple types of therapeutic interventions (e.g., gene therapies, gene editing, antisense oligonucleotides, direct protein or small molecule delivery, and use of other novel nucleic acid therapies) to neuronal cell-derived models as well as performing various subsequent assessments to those models based on the needs of the sponsor (e.g., RT-qPCR quantification of UBE3A-ATS and UBE3A RNA levels, immunostaining for UBE3A protein levels and its subcellular localization, and functional assays including calcium imaging and ubiquitination testing). The Keung lab also has capabilities to perform RNAseq and single cell RNAseq to assess transcriptional responses and alterations in cell type compositions of 2D culture and 3D organoids in response to perturbations.