HEART ATTACK: mRNA used to repair and regenerate cardiomyocytes

The new technology uses synthetic messenger ribonucleic acid (mRNA) to deliver mutant transcription factors, or proteins that control the conversion of DNA to RNA, to the hearts of mice. Until then, “no research team has been able to achieve such a result,” comments lead author Dr. Robert Schwartz, Professor of Biology and Biochemistry.

Synthetic mRNA drives cell regeneration

A first in vitro proof: lSynthetic mRNA contributes to cell growth by delivering 2 mutant transcription factors, Stemin and YAP5SA, that work together to increase replication of cardiomyocytes, or cardiomyocytes isolated from mouse hearts. At this stage, the demonstration is carried out in vitro on tissue cultures. By dedifferentiating the cardiomyocytes into a more stem cell-like state, it can regenerate and multiply: the Stemin transcription factor activates the stem cell-like properties of the cardiomyocytes. YAP5SA promotes and accelerates cardiomyocyte replication.

Another in vivo proof: Stemin and YAP5SA finally make it possible to repair damaged mouse hearts in vivo: myocyte nuclei replicated at least 15 times within 24 hours after cardiac injections that delivered these transcription factors: “Injection of the two transcription factors into mouse hearts led to astonishing results. The cardiomyocytes proliferated rapidly within a day and a month later the hearts were repaired and exhibiting almost normal cardiac pumping function with very little scarring.”

More controllable delivery: Another benefit of synthetic mRNA is that, unlike viral transmission, it disappears within a few days. Gene therapies delivered to cells by viral vectors raise several biosafety issues because they cannot be easily stopped. mRNA-based delivery, on the other hand, quickly reverses and disappears.

These results are particularly important because

less than 1% of adult heart muscle cells regenerate over the course of life.

“Most people die with the same cardiomyocytes they had in the first month of life. During a heart attack, heart muscle cells die and the heart can lose its ability to contract.

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