Snow, K. J.; Saville, E.; Heffner, C.; Gaitan, Y.; Duryea, J.; Davis, T. L.; Bechtel, L.; Hannigan, S.; Low, B. E.; Rossius, J.; Dang, T.; Kulhankova, K.; Cheng, A. X.; Wiles, M. V.; Wurst, W.; McCray, P. B.; Guay, D.; Lutz, C. M.; Bergstrom, D. E.; Kuehn, R.; Murray, S. A.

With the expansion of therapeutic gene editing technology, small animal models provide essential platforms to evaluate the function of these new approaches in vivo. As part of the Somatic Cell Genome Editing (SCGE) Consortium, we developed next-generation murine reporters that overcome current model limitations and broaden detectable in vivo editing outcomes. These include two mouse models built on the ''traffic light'' reporter concept. This system enables fluorescent detection of both gene repair (green) and CRISPR-generated indels (red) events following editing by a single guide and either dsDNA or single-stranded oligonucleotide donor. We also generated a third reporter model that efficiently detects A-base editor activity. Reporters were validated in cultured embryos, via germline editing, and through activation in vivo by AAV transduction or direct ribonucleoprotein delivery. Together, these new models provide a valuable resource for improved detection of genome editing events in vivo.