Tel Aviv University‘s researcher team designed a new technique of conveying RNA-based medications to a subpopulation of immune cells engaged in the inflammatory process and target the disease-inflamed cell without causing damage to other cells.
The revolutionary technology may improve the treatment of cancer and a wide spectrum of diseases and medical ailments.
The study, published in the prominent scientific journal Nature, was led by Prof. Dan Peer, a global pioneer in the development of RNA-based medicinal delivery. He is Tel Aviv University’s Vice President for Research and Development, head of the Center for Translational Medicine.
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Prof. Peer explained “Our development 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. We have now taken out of the equation healthy cells that can help us, 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.”
Prof. Peer and his colleagues could show this ground-breaking finding in animal models of inflammatory bowel disorders such as Crohn’s disease and colitis and significantly improve all inflammatory symptoms without manipulating around 85 percent of immune system cells. The new development is based on a straightforward concept: it targets a certain 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,” explains Prof. 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.”
Prof. Peer and his team previously developed the most advanced delivery system of its kind based on fatty nanoparticles; this method has already gained clinical approval for the administration of RNA-based therapeutics to cells. They are now attempting to further refine the delivery mechanism.
Prof. Peer believes that the new discovery could have consequences for a wide variety of diseases and medical conditions.
“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. We now know how to wrap RNA in fat-based particles so that it binds to specific receptors on target cells,” he says. “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.”
Prof. Peer adds, “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 involving 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. 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.”
