CRISPR gene editing could protect cardiac tissue from damage caused by a stroke or heart attack, according to research published in the journal Science.
Currently, CRISPR-Cas9 gene editing is typically used to correct specific genetic mutations before the onset of disease, with treatment usually offered to a limited group of affected patients.
But researchers found that the gene editing technique could also potentially act as a cardioprotective strategy applicable to a wide range of patients with heart disease.
The team used CRISPR-Cas9 gene editing to target the oxidative activation sites of calmodulin-dependent protein kinase IIδ (CaMKIIδ), which is a primary driver of cardiac disease.
Injecting the gene editing agent protected mice from ischemia/reperfusion injury, in which tissue damage occurs when blood supply is restored following a period of restricted oxygen.
Importantly, CaMKIIδ editing soon after exposure to ischemia enabled the mice to recover from severe heart damage, suggesting it might not be too late to intervene after a heart attack has occurred.
The researchers say that CaMKIIδ gene editing may therefore represent a permanent and advanced strategy for heart disease therapy.
Senior researcher Eric Olson, a professor at the University of Texas Southwestern Medical Center, told Inside Precision Medicine how the research might expand current applications in the field.
“CRISPR gene editing is being developed to correct monogenic mutations that cause serious hereditary diseases in relatively small numbers of patients,” he explained.
“This paper describes a complementary approach that is potentially applicable to larger numbers of patients by inactivating a disease-causing signaling pathway.
“The method has high specificity for the injured heart and thereby avoids some concerns with systemic delivery of gene editing therapies and also requires much lower doses of the viral delivery vehicle.”
He said it was now necessary to optimize the method used, carry out further safety studies and possibly develop non-viral delivery methods with higher efficiency.
The study showed that editing the CaMKIIδ gene to eliminate oxidation-sensitive methionine residues protected cardiomyocytes derived from human induced pluripotent stem cells from ischemia/reperfusion injury.
Mouse studies then revealed that CRISPR-Cas9 gene editing of CaMKIIδ at the time of this type of injury could enable the heart to recover function from otherwise severe damage.
“In patients, administration of CaMKIIδ editing components after a myocardial infarction could be achieved in conjunction with the standard of care in response to a heart attack,” the researchers propose.
“The first therapeutic step after a myocardial infarction is coronary angiography and revascularization of the infarct artery, which requires a catheter that could also be used to deliver CaMKIIδ editing components to the infarct artery or to the infarct area.”
