Microprobe-Integrated Human Organoid Arrays to Study AS Genotypes and Therapeutics”

In the process of developing novel therapeutics for Angelman syndrome (AS) several challenges exist that can hinder the process and speed of treatment discovery. These include 1) AS models in animals do not fully mimic the disease in humans and hence accurate assessment of the effectiveness of a putative treatment is difficult; 2) animal studies are time consuming and expensive: 3) AS is molecularly diverse, and experimental and screening models do not capture a large proportion of patient genotypes; and 4) high throughput sensor platforms for rapid screening of direct therapeutic effects on neuronal function are needed. This work aims to address these key challenges that hinder the development of new therapeutics for AS by developing a method to embed micro-sensors within organoids and use them to measure functional phenotypes of large deletion, mutation, and uni parental disomy AS organoids. Optimization of this sort of high throughput screening platform will be beneficial to rapidly study the efficacy of new emerging therapeutics for AS, and determine specific responses of each distinct AS genotype.