Described herein are methods and compositions useful for inducing maturation of a cardiomyocyte to a mature (e.g., adult) phenotype, such that the function and morphology of the mature cardiomyocyte matches or more closely mimics that of the adult heart. The methods and compositions use Let-7 miRNAs and modified forms thereof. Such methods and compositions permit the study and treatment of adult-onset cardiac diseases, disorders or injuries with mature cardiomyocytes that mimic the heart function of an adult. Methods of using cardiomyocytes matured in this manner for drug identification and drug cardiotoxicity testing are also provided.