CRISPR Could Identify Heart Disease Risk Long in Advance

Our genome contains many gene variants (genetic changes) that determine susceptibility to disease. For many of these variants, a direct connection with disease has not yet been identified; their effects are still based on predictions. A very important study that could change this was conducted using the gene-editing CRISPR genetic technology . In June 2018, a study published in “Circulation”combined CRISPR for the first time with stem cell technology to examine a genetic variant’s role in increasing heart disease risk. This study could shed light on revolutionary developments in precision medicine.

The DNA of 54 healthy people without heart disease was analyzed with next-generation sequencing to examine genes linked to hypertrophic cardiomyopathy. Known as pathological heart enlargement , hypertrophic cardiomyopathyresults from pathological thickening of the heart muscle. It is among the most common hereditary heart diseasesand is responsible for sudden heart attacks in young people, particularly young athletes.

In the 54 people analyzed, 592 gene variants were found. Of them, 78 percent were classified as benign (harmless). In 17 patients, variants classified as “likely pathogenic (harmful)” were found.

In one participant, researchers identified a variant in the MYL3 geneassociated with hypertrophic cardiomyopathy. This MYL3 variant also occurred in other family members, but they showed no irregular heartbeat or heart muscle enlargement.

Researchers took the participant’s blood cells and converted them into induced pluripotent stem cells, genetically reprogrammed to become embryonic stem cells again. These can generally develop into different cell types. Using CRISPR gene editing, the MYL3 variant in these cells was made recessive. The stem cells were then converted into heart muscle cells, allowing analysis of whether the variant was pathogenic or harmless in them.

Analysis found the participant’s variant benign. Researchers also examined whether unwanted mutations occurred in CRISPR-edited heart cells. No off-target mutations were found.

So What Does This Study Mean for Us?

• This is an important development in precision/personalized medicine. The technique could determine what health problems a variant of uncertain clinical significance might cause. Instead of waiting a long time to see whether disease develops, it could predict whether a variant is dangerous.
• CRISPR, considered one of the century’s most important discoveries, was used in this study. Contrary to concerns, no off-target mutations were observed in genetically modified cells. CRISPR is becoming safer and more effective every day.
• It should be emphasized that this study involved a single patient. Growing stem cells and performing the analyses took 6 months. The technique needs validation in more participants.
• Genetics is experiencing a golden age in modern medicine. Last year, a study in Naturecorrected a hereditary heart disease mutation in human embryos using CRISPR. CRISPR will be one of precision medicine’s most important tools.