“The Pitt team is using mRNA instead to essentially turn back time in injured organs. ‘What we’re proposing to do with mRNA is use it to deliver proteins that have the capacity to repair those damaged liver cells,’ Weissman says. ‘Our hope is that we can treat end-stage liver disease and turn the livers around, maybe forever, or at least until patients can get a transplanted organ liver.’ Instead of delivering instructions for a foreign protein to generate an immune response, they’re delivering the genetic code for producing a transcription factor—HNF4 alpha.

In a paper published in 2021, the approach revived human liver cells in lab dishes. The researchers have since tested the mRNA therapy in rats with cirrhosis and liver failure. They treated a group of rats every three days for three weeks while a second group served as a control. The animals that were receiving the injection of HNF4 alpha started being more active. The untreated rats continued to decline and eventually died, the expected result at their stage of disease. Some of the treated rats were still living six weeks after receiving the mRNA medicine…

The team is also testing the mRNA infusions in human livers removed from patients undergoing transplants—the process I got to observe. Unlike live rats, explanted human livers can’t be observed for weeks on end. Livers have to be retrieved quickly and infused with the mRNA treatment soon after they’re removed from the body. They stay fresh for just four days or so in a preservation fluid. Six hours after the mRNA infusion, levels of HNF4 alpha start going up and last for two to three days. When HNF4 alpha peaks, other essential liver proteins, such as albumin, start to increase as well. That’s important, Soto-Gutiérrez says, because maintaining those protein levels could mean the difference between a patient needing a transplant or not.”

From Wired.