Israel makes major breakthrough in treating cancer without harming healthy cells
A major problem in cancer treatments is that many of them destroy the malignant cells but also harm healthy cells nearby.
Tel Aviv University (TAU)researchers have developed a groundbreaking technology in which – for the first time in the world – they have made possible the targeted delivery of therapeutic RNAs only to cancer cells, with no harm caused to healthy ones.
Ribonucleic acid (RNA) is an important biological macromolecule that is present in all biological cells and is involved mainly in the production of proteins, carrying the messenger instructions from DNA – which itself contains the genetic instructions required for the development and maintenance of life.
The conventional view of RNA casts the molecule in a only a supporting role – and that’s how the most familiar form of RNA – messenger RNA – works. But only a small fraction of RNA molecules in cells are mRNAs.
As well as carrying instructions for making proteins, RNAs help to turn genes on and off, assist in carrying out chemical reactions, slice and dice other RNAs and even build proteins by transporting amino acids and linking them together. Many RNA therapies are in the development pipeline, with around a dozen already being tested in clinical trials.
Tel Aviv University’s groundbreaking technology may revolutionize the treatment of cancer and a wide range of diseases and medical conditions. The study was led by Prof. Dan Peer, a global pioneer in the development of RNA-based therapeutic delivery and TAU’s vice president for research and development, head of the center for translational medicine and a member of both the Shmunis School of Biomedicine and Cancer Research in the Wise Faculty of Life Sciences and the Center for Nanoscience and Nanotechnology. The study was published in the prestigious scientific journal Nature under the title “Conformation-sensitive targeting of lipid nanoparticles for RNA therapeutics.”
In the framework of this study, the researchers were able to create a new method of transporting RNA-based drugs to a sub-population of immune cells involved in the inflammation process and target the disease-inflamed cell without causing damage to other cells.
“Our development actually changes the world of therapeutic antibodies. Today we flood the body with antibodies that, although selective, also damage healthy cells,” Peer explained. “We have now removed the uninfected cells from the equation, and – via a simple injection –succeeded in targeting only the cells that are inflamed at that given moment.”
Peer and his team were able to demonstrate this major 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,” continued 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.”
Previously, the TAU team developed delivery systems based on fatty nanoparticles – the most advanced system of its kind that has 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.
The discovery has possible implications for a wide range 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,” Peer said.
“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.”
The TAU researchers were able to organize the delivery system in such a way that they targeted only 14.9% of the cells that were involved in the inflammatory condition of the disease without harming the other, non-involved, cells that were completely healthy.
“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,” he concluded. “In other words, we were able to deliver the drug ‘door-to-door,’ directly to the diseased cells.”
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