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B - Gene Targeting and Gene Correction -> B1 – Gene Targeting and Gene Correction – In Vivo Studies (Basic development of novel technologies for genome editing, with or without site-specific endonuclease.

504: Development and Characterization of New Reporter Mouse Models for In Vivo Gene Editing

Type: Poster Session

Poster Board Number: 504
Presentation Details
Session Title: Wednesday Poster Session
Start Time: 5/17/2023 12:00
End Time: 5/17/2023 14:00

With the evolution and expansion of therapeutic CRISPR/Cas9 gene editing technologies, reliable, efficient small animal models are needed to evaluate the function of these new tools in vivo. To improve on existing reporters such as Ai9, JAX’s Small Animal Testing Center (SCGE Consortium) has developed several new gene editing reporter alleles based on a “traffic light” reporter design. The new reporters can be used to detect a variety of DNA repair outcomes following editing with a single guide, including non-homologous end joining (NHEJ), homology-directed repair (HDR) and base editing. These models include PAM sites for multiple Cas9 variants, and in some cases have been designed to bias repair outcomes to improve the rate of reporter activation following an editing event. Each reporter line has been characterized for both baseline reporter functionality in cultured mouse embryos, and has been validated in for in vivo somatic gene editing applications through extensive characterization of a standard panel of adult tissues. Together, these new models provide a valuable resource for improved detection of genome editing events and expands the breadth of nucleases and editing outcomes that can be tested in vivo.

Kathy J. Snow1, Caleb Heffner1, Yaned Gaitan1, Ethan Saville1, Lawrence Bechtel1, Tiffany L. Davis1, Wolfgang Wurst2, Ralf Kuehn3, Stephen A. Murray1, David E. Bergstrom1

1The Jackson Laboratory, Bar Harbor, ME,2Helmholtz Centre Munich, Neuherberg, Germany,3Max Delbruck Center for Molecular Medicine, Berlin, Germany
 K.J. Snow: None.

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