New TAU method delivers therapeutic RNAs exclusively to cancer cells – Innovita Research

New TAU method delivers therapeutic RNAs exclusively to cancer cells

Researchers at Tel Aviv University have created a new method of transporting RNA-based drugs to a subpopulation of immune cells involved in the inflammation process, and target disease-inflamed cells without causing damage to healthy cells that surround them. The new technology may revolutionize the treatment of cancer and a wide range of diseases and medical conditions.

The study was led by Professor Dan Peer, a global pioneer in the development of RNA-based therapeutic delivery. He is TAU’s Vice President for Research and Development, head of its Center for Translational Medicine and a member of both the Shmunis School of Biomedicine and Cancer Research at the George S. Wise Faculty of Life Sciences and the Center for Nanoscience and Nanotechnology. The study was published in the journal Nature.

“Our development actually changes the world of therapeutic antibodies,” Professor Peer explains. “Today we flood the body with antibodies that, although selective, damage all the cells that express a specific receptor, regardless of their current form. 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 we can silence, express, or edit a particular gene exclusively in the cells that are inflamed at that given moment.”

Professor Peer and his team were able to demonstrate this groundbreaking development in animal models of inflammatory bowel diseases such as Crohn’s disease and colitis, and improve all inflammatory symptoms without performing any manipulation on about 85% of the immune system cells. Behind the innovative development stands a simple concept: targeting to a specific receptor conformation.

“On every cell envelope in the body, that is, on the cell membrane, there are receptors that select which substances enter the cell,” says Professor Peer. “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. But some of these receptors are dynamic — they change shape on the membrane according to external or internal signals.

“We 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.”

In the past, Professor Peer and his team developed delivery systems based on fatty nanoparticles. The systems were the most advanced of their kind; they have already received clinical approval for the delivery of RNA-based drugs to cells. Now, they are trying to make the delivery system even more selective.

“Our development has implications for many types of blood cancers and various types of solid cancers, different inflammatory diseases, and viral diseases such as the coronavirus,” according to Professor Peer. “We now know how to wrap RNA in fat-based particles so that it binds to specific receptors on target cells. But the target cells are constantly changing. They switch from ‘binding’ to ‘non-binding’ mode in accordance with the circumstances.

“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. We tested the protein we developed in animal models of inflammatory bowel disease, both acute and chronic.”

“We were able to organize the delivery system in such a way that we target to 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,” Professor Peer reports. “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. 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. In other words, we were able to deliver the drug ‘door-to-door,’ directly to the diseased cells.”

The study was led by Professor Peer and Dr. Niels Dammes, a postdoctoral fellow from the Netherlands, with the collaboration of Dr. Srinivas RamishettiDr. Meir Goldsmith, and Dr. Nuphar Veiga of Professor 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).

Source: AFTAU