September 28, 2022

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In vivo repair of cardiac fibrosis: mRNA technology shows new potential

In vivo repair of cardiac fibrosis: mRNA technology shows new potential



 

In vivo repair of cardiac fibrosis: mRNA technology shows new potential. 

Heart disease has always been the main killer of mankind. Cardiac fibrosis is a common type of heart disease that causes a large number of deaths every year.

In early January of this year, researchers at the University of Pennsylvania in the United States developed a new treatment for heart disease through CAR-T therapy and mRNA technology, which instantly exploded the circle of friends.

 

CAR-T therapy and mRNA technology to help the treatment of cardiac fibrosis

In vivo repair of cardiac fibrosis: mRNA technology shows new potential

 

The new study, led by Dr. Jonathan Epstein, a professor at Penn’s Center for Cardiovascular Research , was published in the journal Science .

According to Epstein, they have established a company to specifically advance this work. The company’s name is Equity in Teefib, a biotechnology company focused on CAR-T treatment of fibrosis. But there is very little information about the company.

 

In vivo repair of cardiac fibrosis: mRNA technology shows new potential
Jonathan Epstein

 

“Almost all heart disease is accompanied by fibrosis,” Epstein said. “This fibrotic scar tissue prevents the heart from relaxing and contracting, directly causing nearly half of all heart failures.

Tissue fibrosis also contributes to lung and kidney disease. The main cause, but there is currently no effective treatment.”

 

So far, the treatment has only been tested in mice, but it holds great promise for millions of people whose heart muscle has been damaged by fibrosis.

 

 

The technology behind the new therapy

Next, we briefly introduce CAR-T therapy and mRNA technology, and then introduce the results of this research.

In the traditional leukemia treatment, there is a very effective targeted therapy CAR-T (chimeric antigen receptor T cell) therapy, which can genetically modify the immune cells in the patient to translate specific glycoproteins to recognize tumor cells.

It allows the immune cells in the body to accurately identify cancer cells, just like wearing a specific lock. When the cells find the key on the cancer cells, they can accurately kill the cancer cells without accidentally injuring a large number of normal cells.

So, what about mRNA technology?

We all know that DNA is composed of four base-pairing double helices. During its replication and transcription, after DNA unwinding, two single strands are produced, which are complementary to the bases on one of the single strands, and synthesize mRNA chain, and then the ribosome recognizes the base combination on the mRNA, and then synthesizes the amino acid into the peptide chain, and the peptide chain is twisted and folded under the action of the endoplasmic reticulum and the Golgi apparatus. .

During the Covid-19 pandemic, mRNA vaccines have come into prominence, stimulating cells to produce a specific glycoprotein often found on the surface of Covid-19, which acts like a specific key. The human immune system is familiar with this “key” through repeated injections of vaccines, it will precisely match this key, and then kill the cells that have this “key”.

When people are actually attacked by a virus, the immune system recognizes the virus that holds the “key”.

 

There is a lot of room for new treatments

Last year, more than one billion people around the world received mRNA COVID-19 vaccine, and mRNA showed good tolerance and success rate. In fact, scientists are thinking, can mRNA technology be used to treat more diseases?

 

In vivo repair of cardiac fibrosis: mRNA technology shows new potentialCAR-T therapy for cardiac fibrosis

In Epstein’s study, they applied the idea of ​​CAR-T to specifically identify cells, and also referred to the idea of ​​mRNA producing a specific “key” in the body.

The difference is that the treatment conceived by Epstein is done in vivo, which greatly increases the universality of this treatment compared to CAR-T that needs to be edited in vitro.

In fact, the new treatment partner, University of Pennsylvania professor Carl June (Carl June) is also one of the founders of CAR-T therapy, and he is also one of the corresponding authors of the paper.

This research was also prompted by chance. One of Epstein’s graduate students at the time believed that CAR-T could treat cardiac fibrosis.

A few days later, Epstein met Juno in the elevator and discussed it with him.

 

In vivo repair of cardiac fibrosis: mRNA technology shows new potentialComparison of in vitro (top) and in vivo (bottom) generation of CAR-T cells

 

In the treatment of myocardial fibrosis, mRNA induces cells to produce glycoproteins on the surface of fibrotic cells, and then allows immune cells to destroy these fibrotic cells.

Compared with CAR-T directly editing T cells, mRNA is safer and more efficient because genes are Edited T cells exist in the body for a long time and may attack other cells, but mRNA technology does not have this risk, because mRNA survives in the body for a short time.

 

With PET, we can see where the heart is damaged

And thanks to the rapid development of imaging technology, the treatment process of fibrosis can be seen in real time.

Still, there are many risks, and there is a long way to go to treat cardiac fibrosis with this approach, Epstein said.

They next plan to conduct large mammal experiments, preferably in the clinic within two years, to develop more appropriate doses and appropriate treatments.

Epstein said, “I am very happy that there is a lot of room for this kind of treatment now. Unlike cancer treatment, doctors do everything they can to kill all cancer cells to avoid recurrence.

But with tissue fibrosis, any A small cure can greatly improve a patient’s life.

Although it will take a long time to reach the clinic, this experiment also proves that the potential of mRNA extends beyond the COVID-19 vaccine. “

Drew Weissman , a scientist at the University of Pennsylvania , is one of the pioneers of mRNA technology and an “iron powder.” He said that mRNA is currently being used as an experimental vaccine for HIV.

 

In addition to the AIDS vaccine, mRNA technology has been used in many vaccines, such as the prevention of influenza, shingles, respiratory syncytial virus, and even in the treatment of cancer.

“The potential of RNA is endless, and the future will be the world of RNA,” Weisman said.

 

 

References
1.https://www.dispatch.com/story/news/healthcare/2022/02/04/covid-vaccine-mrna-technology-offers-hope-heart-disease-treatment/6597434001/
2.https://www.science.org/doi/10.1126/science.abm0594

In vivo repair of cardiac fibrosis: mRNA technology shows new potential

(source:internet, reference only)


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