LAUSR

Major advances in gene editing using CRISPR have improved accessibility for the creation of disease relevant in vitro models, allowing researchers to readily interrogate oncogenic driver mutations and elucidate novel targets to overcome challenges within cancer research such as drug resistance. Despite this, the rapid generation of disease relevant cell lines at the scale needed for successful and efficient therapeutic development remains challenging in part due to the sheer number of potential oncogenic driver mutations and cancer targets along with using traditional manual approaches. Specific challenges include: the efficient generation of gene knockouts and corresponding loss of protein; efficient knock-in of gene tags and single nucleotide variants; and controlling the zygosity of these genetic outcomes. To address these limitations, we describe the use of our automated, high throughput CRISPR editing platform, ECLIPSE, for the rapid generation of cell models such as immortalized cells and induced pluripotent stem cells. We leveraged our chemically modified synthetic sgRNAs, optimized nucleofection methods, and automated pipelines for the generation of CRISPR-edited cells at various scales to address the needs of researchers. This scale ranges from individual edited cell clones for drug target validation to the generation of hundreds of knockout cell pools in a ready-to-assay arrayed format for gene target identification in drug screening. The utilization of automated systems such as the ECLIPSE platform are critical catalysts for the rapid generation of engineered cell lines at relevant scales to address the challenges of cancer research. Citation Format: Peter Deng, Matthew Rowe, Anna King, Dana Sailor, Antinea Chair, Montse Morell, Andreia G. Sommer, Kevin Holden. Eclipse, an automated CRISPR platform for the large-scale generation of cell models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6508.