Cedars-Sinai researchers have developed an experimental RNA-based drug, TY1, which has shown potential in repairing DNA and healing tissue damage. The findings were published in Science Translational Medicine.
"By probing the mechanisms of stem cell therapy, we discovered a way to heal the body without using stem cells," said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai and senior author of the study. "TY1 is the first exomer—a new class of drugs that address tissue damage in unexpected ways."
TY1 is a synthetic version of an RNA molecule naturally present in the body. Researchers demonstrated that TY1 boosts the activity of TREX1, a gene that enables immune cells to clear away damaged DNA. This process supports tissue repair.
The development process began over twenty years ago when Marbán's team at Johns Hopkins University isolated progenitor cells from human heart tissue. Unlike stem cells, these progenitor cells focus on regenerating specific tissues such as heart muscle after injury.
At Cedars-Sinai, Ahmed Ibrahim, PhD, MPH, found that heart progenitor cells release exosomes—small sacs containing RNA molecules—that aid in repairing injured tissue. "Exosomes are like envelopes with important information," said Ibrahim, associate professor in the Department of Cardiology at the Smidt Heart Institute and first author of the paper. "We wanted to take apart these coded messages and figure out which molecules were, themselves, therapeutic."
Through genetic sequencing of exosome contents, scientists identified one RNA molecule more abundant than others and effective in promoting healing after heart attacks in laboratory animals. TY1 was engineered to replicate this natural molecule’s structure while aligning with existing approved RNA drugs.
The research team observed that TY1 increases production of immune cells capable of reversing DNA damage—a mechanism believed to reduce scar formation following heart attacks. "By enhancing DNA repair, we can heal tissue damage that occurs during a heart attack," Ibrahim said. He added: "We are particularly excited because TY1 also works in other conditions, including autoimmune diseases that cause the body to mistakenly attack healthy tissue. This is an entirely new mechanism for tissue healing, opening up new options for a variety of disorders."
Researchers plan to move forward by testing TY1 in clinical trials.
