ECLIPSE, An Automated CRISPR Platform for the Large-Scale Generation of Cell Models for the iPSC Neurodegenerative Disease Initiative (iNDI)

The National Institutes of Health led iPSC Neurodegenerative Disease Initiative (iNDI) is the largest iPSC genome engineering project attempted with the goal of generating a widely available and standardized set of diseased cell models for over 100 single nucleotide variants (SNV) mutations associated with Alzheimer’s disease and related dementias (ADRD) in isogenic IPSC lines. The standardization of cell models is of vital importance for the generation of reproducible and actionable data in therapeutic development. As part of a multi-institution collaboration, Synthego was selected for the generation of 25 SNVs in the candidate KOLF2.1 iPSC line. Toward these goals, we describe the use of our automated, high throughput CRISPR editing platform, ECLIPSE, for the rapid generation of knock-in iPSC models of ADRD. We leveraged our state-of-the-art knock-in methods and automated pipelines for the design, experimental optimization, and clonal isolation of 23 of the candidate target mutations in iPSCs. For each SNV target, 3 clonal homozygous and 6 clonal heterozygous mutation lines were generated for a total of 264 clonal cell lines over a 6-month period. The utilization of automated systems such as our ECLIPSE platform are critical catalysts for the rapid development of relevant cell models in large scale disease initiatives such as iNDI.