Genotype and phenotype validation of an isogenic human iPSC-derived neuronal model of Huntington’s Disease

In research and drug discovery for neurological disease, patient-derived induced pluripotent stem cells (iPSCs) offer the possibility to generate in vitro models that can recapitulate relevant human disease phenotypes. However, conventional human iPSC (hiPSC) differentiation protocols are often lengthy, inconsistent, and difficult to scale.

To overcome these problems, we developed a proprietary gene targeting strategy (opti-ox^TM) that enables highly controlled expression of transcription factors to rapidly reprogram hiPSCs into defined somatic cell types. CRISPR-Cas9 genetic engineering was used to introduce a 50 CAG repeat expansion in the huntingtin (HTT) gene of the opti-ox enabled parental cell line to generate a Huntington’s disease model.

This scientific poster shows data validating both the genotype and phenotype of these cells, including gene and protein expression profiles, and electrophysiological analysis in comparison to an isogenic control. 

In this poster, you will explore:

• How ioGlutamatergic Neurons HTT 50CAG/WT were generated using opti-ox precision cellular reprogramming and CRISPR-Cas9 genome engineering
• Data describing the genotype and phenotype of these cells, including RT-qPCR, ICC, Bulk-RNA seq and MEA, all in comparison to an isogenic control
• How ioGlutamatergic Neurons HTT 50CAG/WT form a powerful next-generation model to study Huntington’s disease in research and drug discovery

View poster