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In world-first, Israeli researchers develop technology to fight cancer, other diseases without harming healthy cells

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Tel Aviv University’s Prof. Dan Peer says the new method is able to deliver RNA-based drugs “door-to-door,” directly to diseased cells, without harming healthy cells in the body

By ILANIT CHERNICK

In a world-first, Tel Aviv University (TAU) researchers have developed groundbreaking technology that could revolutionize cancer treatment and numerous other diseases. 

The researchers were able to design a new way of transporting RNA-based drugs to a subpopulation of immune cells involved in the inflammation process and target the diseased or cancerous cells without causing any damage to other healthy cells in the body.

According to TAU’s Prof. Dan Peer, who led the study and is also a well-known pioneer in the world of RNA-based therapeutic delivery their method “actually changes the world of therapeutic antibodies.” 

“Today we flood the body with antibodies that, although selective, damage all the cells that express a specific receptor, regardless of their current form,” he explained. “We have now taken out of the equation healthy cells that can help us, that is, uninflamed cells, and via a simple injection into the bloodstream can silence, express, or edit a particular gene exclusively in the cells that are inflamed at that given moment.”

Using animal models to show the effectiveness of their new medical technology, Peer and his team were able to “improve all inflammatory symptoms” of inflammatory illnesses like Crohn’s Disease “without performing any manipulation on about 85% of the immune system cells.”

Peer pointed out that every cell membrane has receptors that select which substances enter the cell.

“If we want to inject a drug, we have to adapt it to the specific receptors on the target cells, otherwise it will circulate in the bloodstream and do nothing,” he said. “But some of these receptors are dynamic – they change shape on the membrane according to external or internal signals.”

He stressed that his team “are the first in the world to succeed in creating a drug delivery system that knows how to bind to receptors only in a certain situation, and to skip over the other identical cells, that is, to deliver the drug exclusively to cells that are currently relevant to the disease.”

Peer said that their discovery could assist in treating many types of blood cancers and various types of solid cancers, different inflammatory diseases, and even viral diseases such as coronavirus. 

“We now know how to wrap RNA in fat-based particles so that it binds to specific receptors on target cells,” he said. “But the target cells are constantly changing. They switch from ‘binding’ to ‘non-binding’ mode in accordance with the circumstances.” 

Explaining this concept further, Peer said that “if we get a cut, for example, not all of our immune system cells go into a ‘binding’ state, because we do not need them all in order to treat a small incision. 

“That is why we have developed a unified protein that knows how to bind only to the active state of the receptors of the immune system cells,” he highlighted. “We tested the protein we developed in animal models of inflammatory bowel disease, both acute and chronic.”

Discussing how the method works, Peer said that he and his team were able to organize the delivery system of the RNA-based drugs in a way that targeted only 14.9% of the cells that were involved in the inflammatory condition of the disease, “without adversely affecting the other, non-involved, cells, which are actually completely healthy cells.” 

“Through specific binding to the cell sub-population, while delivering the RNA payload we were able to improve all indices of inflammation, from the animal’s weight to pro-inflammatory cytokines, [which are a group of proteins related to the immune response],” he said. “We compared our results with those of antibodies that are currently on the market for Crohn’s and colitis patients and found that our results were the same or better, without causing most of the side effects that accompany the introduction of antibodies into the entire cell population.”

Concluding, Peer stressed that this means their method is “able to deliver the drug ‘door-to-door,’ directly to the diseased cells.”

 The study was led by Prof. Peer, together with Dr. Niels Dammes, a postdoctoral fellow from the Netherlands, with the collaboration of Dr. Srinivas Ramishetti, Dr. Meir Goldsmith and Dr. Nuphar Veiga, from Prof. Dan Peer’s lab. Professors Jason Darling and Alan Packard of Harvard University in the United States also participated. The study was funded by the European Union, in the framework of the European Research Council (ERC).

The findings were published in the prestigious scientific journal Nature.

** Video and Featured Image: Courtesy of Tel Aviv University

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