The new technology uses synthetic messenger ribonucleic acid (mRNA) to deliver mutated transcription factors, or proteins that control the conversion of DNA to RNA, to the heart… of mice. Until then, “no research team had been able to achieve such a result” comments the main 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 mutated transcription factors, Stemin and YAP5SA, which work in tandem to increase the replication of cardiomyocytes, or cardiac muscle cells, here isolated from mouse hearts. The demonstration is provided at this stage, in vitro on tissue cultures. Dedifferentiating the cardiomyocyte into a more stem cell-like state allows it to regenerate and proliferate: the Stemin transcription factor activates the stem cell-like properties of 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 in 24 hours after cardiac injections which delivered these transcription factors: “The injection of the 2 transcription factors into mouse hearts produced astonishing results. The cardiomyocytes multiplied rapidly within a day, and a month later the hearts were repaired and showed almost normal heart pumping function, with very little scarring.”
Better controllable delivery: Another advantage of synthetic mRNA is that it disappears within days as opposed to viral delivery. 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 fades away.
These results are particularly important because
less than 1% of adult cardiac muscle cells regenerate during life.
“Most people die with the same cardiomyocytes they already had in the first month of life. In the event of a heart attack, heart muscle cells die and the heart’s ability to contract may be lost.