576. DNA Ends Matter: The Impact of Using CRISPR/Cas9 Variants on DNA Repair Pathway Choices and Editing Profiles at the HBB Locus

Abstract

S230can be expressed in both pluripotent stem cells and differentiated cells from all three major germ layers. This allows for the real-time observation of mutations causing phenotypic differences that can be measured in in vitro tissues and organoids during culture as opposed to defined end points. The live cell and tissue assays on ArrayEdit are compatible with standard screening platforms and a variety of human cell types, thus permitting robust and sensitive detection of differences in proliferation, differentiation and other downstream effects of gene editing. This preclinical platform adds important capabilities to observe editing and selection in situ within complex structures generated by human cells, ultimately enabling optical and other molecular perturbations in the editing workflow that could refine the specificity and versatility of gene editing.