mRNA Technology Now Used Sucessfully to Treat Heart Disease

Combining technologies that proved hugely successful against cancer and in COVID-19 vaccines, researchers at the University of Pennsylvania have shown they can effectively treat a leading cause of heart disease. For now the success has only been achieved in mice, but the milestone offers hope for millions of people whose heart muscle is damaged by scar tissue. There is no effective treatment for this fibrosis, which leads to heart disease, the leading cause of death in the United States, said Dr. Jonathan Epstein, a Penn professor of cardiovascular research who helped lead the new work, published in the journal Science.

In his new research, Epstein reversed fibrosis by re-engineering cells, as has been done with a successful blood cancer treatment called CAR-T. In this case, however, the treatment took place inside the body rather than in a lab dish. The team delivered the treatment using mRNA technology, which has been proven over the last year with hundreds of millions of people receiving mRNA-based COVID vaccines.

If it works (in people), it really could have enormous impact,” Epstein said. “Almost every type of heart disease is accompanied by fibrosis.”

About 50% of heart failure is directly caused by this scar tissue, which prevents the heart from relaxing and pumping effectively. Fibrosis also is involved in leading causes of lung and kidney disease.

Source: https://eu.usatoday.com

How To Uncloak Cancer Cells And Reveal Them To The Immune System

Scientists at Johns Hopkins report they have designed and successfully tested an experimental, super small package able to deliver molecular signals that tag implanted human cancer cells in mice and make them visible for destruction by the animals’ immune systems. The new method was developed, say the researchers, to deliver an immune system “uncloaking” device directly to cancer cells.

Conventional immune therapies generally focus on manipulating patients’ immune system cells to boost their cancer-killing properties or injecting drugs that do the same but often have toxic side effectsA hallmark of cancer biology is a tumor cell’s ability to essentially hide from the immune system cells whose job is to identify and destroy cancer cells. Current cellular immunotherapies, notably CAR-T, require scientists to chemically alter and enhance a patient’s own harvested immune system T-cells — an expensive and time-consuming process, say the researchers. Other weapons in the arsenal of immunotherapies are drugs, including so-called checkpoint inhibitors, which have broad effects and often lead to unwanted immune-system-associated side effects, including damage to normal tissue.

By contrast, the Johns Hopkins team sought an immune system therapy that can work like a drug but that also individually engineers a tumor and its surrounding environment to draw the immune system cells to it, says Jordan Green, Ph.D, professor of biomedical engineering at the Johns Hopkins University School of Medicine.

A microscopic image of the nanoparticles used in the study. The black scale bar is 100 nm in size
 And our process happens entirely within the body,” Green says, “requiring no external manipulation of a patient’s cells.

To develop the new system, Green and his team, including Stephany Tzeng, Ph.D., a research associate in the Department of Biomedical Engineering at Johns Hopkins, took advantage of a cancer cell’s tendency to internalize molecules from its surroundings. “Cancer cells may be easier to directly genetically manipulate because their DNA has gone haywire, they divide rapidly, and they don’t have the typical checks and balances of normal cells,” says Green.

The team created a polymer-based nanoparticle — a tiny case that slips inside cells. They guided the nanoparticles to cancer cells by injecting them directly into the animals’ tumors. “The nanoparticle method we developed is widely applicable to many solid tumors despite their variability on an individual and tumor type level,” says Green, also a member of the Johns Hopkins Kimmel Cancer Center. Once inside the cell, the water-soluble nanoparticle slowly degrades over a day. It contains a ring of DNA, called a plasmid, that does not integrate into the genome and is eventually degraded as the cancer cell divides, but it stays active long enough to alter protein production in the cell.

The additional genomic material from the plasmid makes the tumor cells produce surface proteins called 4-1BBL, which work like red flags to say, “I’m a cancer cell, activate defenses.” The plasmid also forces the cancer cells to secrete chemicals called interleukins into the space around the cells. The 4-1BBL tags and interleukins are like magnets to immune system cells, and they seek to kill the foreign-looking cancer cells.

Results of the proof-of-concept experiments were published online in the Proceedings of the National Academy of Sciences.

Source: https://www.hopkinsmedicine.org/