Editing a gene that drives a series of injuries after a heart attack reverses this inevitable course in mice, leaving the heart remarkably intact, according to a new study by scientists at UT Southwestern University. rice field.Findings published in chemistrymay lead to new strategies to protect patients from the consequences of heart disease.
“Depriving the heart of oxygen for a long period of time, as it normally does in heart attacks, causes great damage to the heart. However, animals whose myocardium has been gene-edited after an induced heart attack can survive for several weeks.” After a few months, it appears to be essentially normal.I co-led the study with Dr. Rhonda Bassel-Duby, Ph.D. in Molecular Biology at UTSW and Professor of Molecular Biology.
Since its discovery ten years ago, the CRISPR-Cas9 gene-editing system has been used by scientists to correct disease-causing genetic mutations, including work by the Olson lab on Duchenne muscular dystrophy. However, Dr. Bussel-Dubie explained that while these diseases caused by mutations affect relatively few people, non-genetic diseases affect far more people. , cardiovascular disease is the leading cause of death worldwide, killing about 19 million people each year.
Researchers recently found that much of the damage from a heart attack, an event characterized by the blockage of blood vessels that feed and deprive the heart of oxygen, CaMKⅡ?. This gene has a variety of roles in cardiac cell signaling and function. Hyperactivation occurs when the heart is stressed and is caused by the oxidation of two methionine amino acids that form part of the heart. cam key? protein.
Doctor. Olson, Bassel-Duby and their colleagues suggested that if these methionines could be converted to other amino acids instead, no oxidation would occur and the heart would cam key? Hyperactivation and Subsequent Damage After Heart Attack.
To test this idea, postdoctoral researcher Simon Lebek, MD, and other members of the team used CRISPR-Cas9 to make edits. cam key? Human heart cells growing in petri dishes. Tests showed that placing unedited heart cells in hypoxic chambers resulted in numerous markers of damage followed by death. However, the edited cells were protected from damage and survived.
The researchers then attempted a similar experiment in live mice, restricting blood flow to the heart’s main pumping chamber for 45 minutes before inducing a heart attack in these animals. cam key? Send gene-editing components directly to the heart of some animals. Both gene-edited and non-edited mice had significantly reduced cardiac function in the first 24 hours after a heart attack. But while the unedited mice continued to get worse over time, the gene-edited mice improved steadily over the next few weeks, eventually becoming nearly indistinguishable from pre-heart attack. achieved cardiac function.
Further research showed that gene editing appeared to be isolated to the heart – there was no evidence of editing cam key? in other organs, including the liver, brain, or muscles. No negative side effects were seen after almost a year of treatment. Olson and Bassel-Duby said: The treatment also appeared to be durable, and gene-edited mice were able to perform strenuous exercise similar to mice that had never had a heart attack.
Adequate safety and efficacy studies are needed before this therapy can be applied to humans, but researchers believe gene editing may offer a promising solution for treating patients after heart attacks. , suggesting the possibility of various other non-genetic disorders. .
“Instead of targeting genetic mutations, we essentially modified normal genes so that they are no longer harmfully overactive. This is a new way of using CRISPR-Cas9 gene editing.” said Dr. Bassel-Duby.
Original: Gene editing stops injury in mice after heart attack in UT Southwest study
Than: University of Texas Southwestern Medical Center
