A new gene-editing technique repairs heart attack damage in mice

A new gene-editing technique repairs heart attack damage in mice

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Gene editing, the technique called CRISPRused to correct defects in genetic diseases, extends its field of action and, according to a study published in the journal “Science”, is capable of modifying a key protein in the hearts of mice that have suffered a heart attack.

According to researchers from the University of Texas (USA), the use of the technique allowed the animals to recover their heart function after suffering a heart attack and could potentially be used in a wide range of patients.

The group led by Eric N. Olson, of the University of Texas Southwestern Medical Center in Dallas (USA), believes this technique could be used to treat a variety of patients with heart disease.

Scientists have used base editors, a CRISPR-derived gene-editing tool, to modify a key protein in mouse hearts in that lesion.

This new approach to the tool CRISPR-Cas9they explain in their work, that targeting a deleterious signaling pathway in the heart confers protection against ischemia/reperfusion injury.

The findings suggest that gene editing could offer an innovative, lifelong strategy to treat heart disease, the leading cause of morbidity and mortality worldwide, and even be employed as an intervention to repair damage immediately after a heart attack.

gene editing CRISPR-Cas9 it has shown promise as a therapeutic approach to treat rare inherited diseases. However, most gene editing strategies focus on correcting specific gene mutations that only occur in a small group of patients and often before disease onset. This means that the application of this therapy continues to be limited.

The researchers sought to assess the role of this innovative gene editing in ischemia/reperfusion (IR) injury, a type of tissue damage that occurs after a variety of cardiovascular injuries, including stroke and heart attack.

Chronic overactivation of a protein (CaMKIIδ) is known to cause several cardiac diseases in humans and mice, including this lesion. This protein is the one that has been manipulated with this technique.

The first therapeutic step after a myocardial infarction is coronary angiography and revascularization or coronary bypass surgery – a medical procedure to improve blood supply to the heart – of the affected artery, which requires a catheter.

According to the researchers, such a catheter could also be used to deliver CaMKIIδ-editing components to the infarct artery or area of ​​the infarct.

This type of CRISPR-Cas9 gene editing, the study authors note, has already been used to knock down the WT PCSK9 gene in the liver as a strategy for hereditary familial hypercholesterolemia. “Our strategy is designed to prevent damage to the adult heart and therefore provide benefits for heart disease. The concept of using CRISPRCas9 to block the activation of deleterious pathways can also be translated to other signals implicated in other human diseases,” they conclude.

For Lluís Montoliu, a researcher at the National Center for Biotechnology (CNB-CSIC) and at CIBERER-ISCIII, Olson’s team “surprises us once again with a new use of the currently most advanced CRISPR tools, base editors, capable of chemically changing letters of the genome (for example, an A for a G) without cutting the DNA and, therefore, with greater security”.

In statements to the Science Media Centre, this expert points out that this first preclinical evidence “suggests that something similar could happen if these same CRISPR reagents were injected into the infarcted area of ​​a human heart, something that will still take time to be investigated.”

But the use of CRISPR tools is not harmless

But the use of CRISPR tools is not harmless.

Thus, the authors of the study acknowledge, “before starting human clinical trials, it is necessary to carry out studies that include plus pharmacological profile analysisoptimization of the viral dose, toxicity and safety of treatment and evaluation of long-term animal survival”.

In addition, they write in their paper, it will also be necessary to analyze the interaction with other drugs and treatments, as well as the effectiveness of gene editing compared to currently available heart failure medication.

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