Heart failure often develops after a heart attack, impacting the heart's ability to maintain energy. This condition affects 6.8 million Americans, with projections indicating that 1 in 4 U.S. adults may develop it during their lifetime, making effective treatments a medical priority. Mitochondria, which are organelles within cells that produce energy, are considered crucial for cardiac recovery.
Heart failure is fundamentally an energy crisis for the heart.
Researchers at Rice University and Baylor College of Medicine have developed a CRISPR-based technique to induce heart cells to increase mitochondrial production to optimal levels, potentially opening a new therapeutic path for heart failure.
Revolutionary CRISPR Approach to Boost Mitochondria
Previous research demonstrated that activating specific genes could increase mitochondrial number and function. However, older strategies often overstimulated cells, leading to cellular malfunction. The current research employs a new technique that controls internal regulatory pathways, enabling cells to safely produce more mitochondria without adverse effects.
CRISPR, or clustered regularly interspaced short palindromic repeats, is a gene-editing technology that targets and modifies specific genes. For this study, researchers developed a non-editing CRISPR system designed to regulate gene expression, functioning as an "on" switch to prompt cells to assemble additional mitochondria.
Precision Control for Cellular Balance
Isaac Hilton, associate professor of bioengineering at Rice, stated that the system's effectiveness is due to its precise control.
"Instead of forcing gene overproduction, CRISPR was used to fine-tune natural regulatory systems in a measured way. This approach enhances mitochondrial performance while preserving cellular balance, a key requirement for safe clinical translation."
Promising Results Across Diverse Models
When tested across various human cell types, the system successfully increased the production of a regulatory protein, which improved mitochondrial function and cellular energy levels. In human cardiomyocytes, the heart cells responsible for pumping contractions, the system enhanced their rate of oxygen consumption, an indicator of improved mitochondrial function.
Similar improvements were observed when the system was tested in an animal model and in adult human heart donor tissue from both normal and diseased hearts.
Paving the Way for New Heart Failure Treatments
Mario Escobar, assistant research professor of bioengineering at Rice and first author of the study, noted that these results are promising for developing future treatments for heart failure and other metabolic diseases.
"These results are promising for developing future treatments for heart failure and other metabolic diseases."
Current treatments for heart failure primarily focus on reducing cardiac energy demand to match an impaired energy supply. Ravi Ghanta, professor of surgery at Baylor, indicated that conventional approaches may lead to additional complications over time because they do not address the underlying energy problem. This research is seen as an important step toward developing effective treatments as heart failure is projected to become more prevalent.
Acknowledgements
The research received support from Baylor College of Medicine, the American Heart Association, and the National Institutes of Health.