The technique uses synthetic messenger ribonucleic acid (mRNA) to deliver mutated transcription factors — proteins that control the conversion of DNA into RNA — to the mouse heart.
The researchers demonstrated that the edited instructions act synergistically through two so-called mutated transcription factors, Stemin and YAP5SA, to increase the replication of cardiomyocytes isolated from mouse hearts. These experiments were performed on in vitro tissue culture dishes. Essentially, this is done to convert cardiomyocytes, which have little regenerative capacity, into a more stem cell-like state so that they can regenerate and proliferate.
“No one has been able to do this before, and we think this technology could be a treatment for [heart disease] in humans,” said biologist Robert Schwartz of the University of Houston.
In experiments in tissue culture dishes and in living mice, Stemin was shown to give cardiomyocytes stem cell-like properties, while YAP5SA promoted heart growth and cardiomyocyte replication. The research team called the process “a game-changer.”
Using live mice, cardiomyocyte nuclei replicated at least 15-fold within 24 hours after injection of the mutant transcription factors Stemin and YAP5SA. “When these two transcription factors were injected into the hearts of adult mice with myocardial infarction, the results were astounding.” Schwartz said the experiments showed that cardiomyocytes rapidly proliferated within one day, and then the following month. , the heart is repaired to close to the pumping function of a normal heart with little scarring.
The researchers reported that synthetic mRNA added to cells disappeared within a few days, just like mRNA produced in our bodies. This gives the new technology an advantage over the gene therapy process, which cannot be easily stopped or removed once started.
Whether this approach can be successfully applied to humans remains to be seen, and it will take years of research to translate it into an effective treatment, but the team is confident.
