Straight to the heart
Courtesy of the researchers
Cardiovascular disease is the leading cause of death worldwide, yet advances in heart-failure therapeutics have stalled. Now, a team of researchers may have opened the door to novel, lifesaving treatments.
At the core of their approach is a human cardiac microphysiological system — also known as a heart-on-a-chip — that provides a miniaturized model of the human heart. Using their system, researchers from UC Berkeley, the Gladstone Institutes and UCSF discovered a lipid nanoparticle that could penetrate dense heart muscle and efficiently deliver therapeutic messenger RNA (mRNA) into heart muscle cells, or cardiomyocytes.
This delivery hinges on something called endosomal escape. The endosome acts as a cell’s sorting station, and if the therapeutic agent gets stuck there, it will degrade. To be effective, the lipid nanoparticle must exit the endosome and enter the cell’s cytoplasm, where it can distribute its mRNA cargo for maximum therapeutic effect.
To tackle this problem, the researchers synthesized lipid nanoparticles with a novel coating, so it could easily diffuse through heart tissue and still exit the endosome. Using their heart-on-a-chip, they tested different iterations to identify the most effective version for delivering the gene-editing therapy to cardiomyocytes.
According to bioengineering professor Kevin Healy, the model’s ability to replicate the complex 3D cellular environments of microtissues could accelerate advances in mRNA cardiac therapies.
“Our framework enables faster, animal-sparing identification of effective lipid nanoparticles for safely delivering these therapies,” said Healy. “We can potentially accelerate programs for heart failure therapeutics, cardioprotective factors and gene correction, while reducing time and cost to translation.”
Learn more: Heart-on-a-chip may lead to new treatments for heart failure; A microphysiological system for screening lipid nanoparticle−mRNA complexes predicts in vivo heart transfection efficacy (Nature Biomedical Engineering)