Intronic CRISPR Repair in a Preclinical Model of Noonan Syndrome–Associated Cardiomyopathy

Hanses U, Kleinsorge M, Roos L, Yigit G, Li Y, Barbarics B, El-Battrawy I, Lan H, Tiburcy M, Hindmarsh R, Lenz C, Salinas G, Diecke S, Müller C, Adham I, Altmüller J, Nürnberg P, Paul T, Zimmermann W-H, Hasenfuss G, Wollnik B, Cyganek L.

Circulation, 2020


Patient specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM’s) were evaluated as a preclinical in vitro model to understand the underlying mechanism of Noonan Syndrome, identify a unique disease-specific proteome signature, and evaluate a personalized therapeutic approach using the CRISPR method. In this study, three out of the four cardiac activity assays available with the Maestro system,  including cardiac field potential, conduction velocity, and contractility, were evaluated to characterize the function and electrophysiology of iPSC-CMs.