After a heart attack, the heart has a hard time recovering and maintaining energy. As a result, one-third of patients develop heart failure. Heart failure affects 6.8 million Americans and carries a high lifetime risk, with one in four adults in the United States expected to develop heart failure during their lifetime. Therefore, finding lasting treatments has become a medical priority.
Because heart failure is essentially an energy crisis of the heart, mitochondria, the organelles that exist within most cells and produce the energy they need to function, may be important allies in recovery. Researchers at Rice University and Baylor College of Medicine used CRISPR-based technology to induce heart cells to increase mitochondrial production to optimal levels, paving the way for new treatments for heart failure.
Previous studies have shown that turning on certain genes increases mitochondrial number and function. However, older strategies overdriven cells, causing them to malfunction. We used a new technique to control internal regulatory pathways, allowing cells to safely generate more mitochondria without burning out. ”
Mario Escobar, assistant professor of bioengineering at Rice University and lead author of the study published in the journal Molecular Therapy
CRISPR (regularly interspaced short palindromic repeats) is a revolutionary gene editing technology that allows targeted editing of specific genes, enabling breakthrough therapies in the treatment of inherited blindness, muscular dystrophy, and most recently, Huntington’s disease.
Researchers have developed a non-editing CRISPR system that specifically controls gene expression and acts as an “on” switch that encourages cells to collect more mitochondria.
“What makes this study so powerful is the level of control,” said Isaac Hilton, associate professor of bioengineering at Rice University and corresponding author of the study.
“Rather than forcing cells to overproduce genes, we used CRISPR to carefully adjust and fine-tune the cells’ natural control systems,” Hilton said. “This allows us to enhance mitochondrial performance while maintaining intracellular balance, a key requirement for safe clinical application.”
When tested in a variety of human cell types, the system was successful in increasing the production of regulatory proteins and amplifying mitochondrial function and cellular energy levels. Importantly, when this system was applied to human cardiomyocytes (heart cells responsible for pump contraction), they improved their oxygen consumption rate, an indicator of improved mitochondrial function. The researchers tested the system in animal models as well as adult heart donor tissue taken from both normal and diseased hearts and found that mitochondrial function was similarly improved.
“These results are very promising for the development of future treatments for heart failure and other metabolic diseases,” Escobar said.
Current treatments for heart failure focus on reducing cardiac energy demand commensurate with energy supply disturbances.
“Traditional approaches do not address the root of the problem and can lead to further complications over time,” said Ravi Ghanta, professor of surgery at Baylor University and co-author of the study. “Heart failure is expected to become more prevalent, so it’s especially important to focus on developing effective treatments. This study is an important step in that direction.”
This research was supported by Baylor College of Medicine, the American Heart Association (917025, 25TPA1463933, 959536), and the National Institutes of Health (R01HL147921, R15HL168688, R01HL166280, R01HL163258, R35GM143532). The contents of this press release are solely the responsibility of the authors and do not necessarily represent the official views of the funding bodies.
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Reference magazines:
Escobar, M. Others. (2026). CRISPR-Cas-based activation of PPARGC1A enhances endogenous mitochondria and enhances cardiac function after myocardial infarction. molecular therapy. DOI: 10.1016/j.ymthe.2026.02.027. https://www.sciencedirect.com/science/article/pii/S1525001626001139
