University of Washington

Xuan Guan

Charles E Murry

Martin K Childers

Michael Regnier

Provided herein are isolated nucleic acids that encode a stable form of Rrm2 for the use of increasing the intracellular Rrm2 protein levels and cytosolic 2-deoxy-ATP (dATP) levels. Further provided herein are methods for treating a cardiac disease or disorder, e.g., myocardial infarction or myocardial ischemia, by administering the isolated nucleic acids, a polypeptide encoded by the isolated nucleic acids, or composition comprising the isolated nucleic acids to a subject in need thereof.

Engineering the RRM2 subunit of ribonucleotide reductase to resist degradation

Methods of screening agents in a cardiomyocyte population are provided. The cardiomyocyte population may be differentiated from a dystrophin knockout iPSC line. High-throughput methods of screening agents in a cardiomyocyte population that has been differentiated from a dystrophin knockout iPSC line are also provided. The methods may include determining an effect of the agents on membrane barrier function by using a cell viability assay. Methods of making dystrophin knockout iPSC lines, making dystrophin knockout iPSC derived cardiomyocytes, and modeling dystrophin deficient cardiomyopathy are also provided.

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Seattle, WA, United States of America

Xuan Guan