Progress in transporting drugs only to cells infected with cancer or viruses without harming healthy ones

Prof. Dan Farr, Tel Aviv University: "Our development actually changes the world of antibodies. Today we flood the body with antibodies that are indeed selective, but also damage the healthy cells. We removed non-inflammatory cells from the game, and with a simple injection we were able to damage only the inflammatory cells at that given moment"

A breakthrough technology from Tel Aviv University may revolutionize the treatment of various types of cancer and a long list of diseases and medical conditions: as part of the research, the researchers were able to produce a new method of transporting RNA-based drugs to a subpopulation of cells of the immune system that participates in the inflammatory process and to attack the cell infected with the disease without causing damage to the other cells.

The research was conducted under the leadership of Prof. Dan Parr, one of the pioneers in the development of RNA-based drug carriers in the world. Prof. Farr is the Vice President for Research and Development, Head of the Center for Translational Medicine and Senior Researcher at the Shmunis School of Biomedical Research and Cancer Research and the Center for Nanoscience and Nanotechnology, in the George S. Wise Faculty of Life Sciences. The study was published in the important journal Nature Nanotechnology.

Prof. Farr: "Our development is actually changing the world of antibodies. Today we flood the body with antibodies that are indeed selective, but damage all the cells that express the receptor - regardless of their current form. We removed from the game healthy cells that can help us, that is, cells that are not inflammatory, and with a simple injection into the blood to silence, express or edit a certain gene only in the inflammatory cells at that given moment."

As part of the research, Prof. Parr and his team were able to demonstrate the groundbreaking development in model animals for inflammatory bowel diseases such as Crohn's disease and colitis - and to improve all the inflammatory indices, without performing any manipulation on approximately 85% of the cells of the immune system.

"On every envelope of a cell in the body, that is, on the cell membrane or the cell membrane, there are receptors that decide which substances will enter the cell," explains Prof. Parr. "If we want to inject a drug, we have to match 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 their shape on the membrane according to external or internal signals. For the first time in the world, we were able to produce a drug delivery system that knows how to bind only to receptors in a certain situation, and ignore the rest of the identical cells, that is, to deliver a drug only to the cells that are currently relevant to the disease."

Prof. Parr and his team previously developed transport systems based on fatty nanoparticles - the most advanced system of its kind that has already received clinical confirmation for the transport of RNA-based drugs into cells. Now, they are trying to make the transportation system even more selective.

The treatment is suitable for the treatment of blood cancer and other types of cancer as well as viral diseases such as the corona virus

According to Prof. Farr, the new breakthrough has possible consequences for a long list of diseases and medical conditions. "Our development has implications for many areas in blood cancers and different types of solid cancers, in various inflammatory diseases and viral diseases such as the corona virus for example. Today we know how to wrap RNA in fat-based particles, so that it binds to the specific receptors on the target cells", Prof. Parr says. "But the target cells are constantly changing. They go from a 'binding' state to a 'non-binding' state according to the circumstances. If we are cut, for example, not all of our immune system cells go into 'binding' mode, because we don't need all of them to treat a small cut. That's why we developed a fusion protein that knows how to bind exclusively to the active state of the receptors in the cells of the immune system. We tested the protein we developed in animal models of inflammatory bowel diseases, both acute and chronic.

Prof. Parr adds: We managed to arrange the transport system so that we changed the RNA of only 14.9% of the cells that were involved in the inflammatory state of the disease - and this without adversely affecting the rest of the non-involved cells, which are actually completely healthy cells. By specifically binding to the cell subpopulation, we were able to improve all measures of inflammation, from animal weight to pro-inflammatory cytokines. We compared our results to the results of antibodies that are on the market today for Crohn's-colitis patients and found that our results were the same or better, without causing most of the side effects associated with the introduction of antibodies into the entire cell population. In other words, we were able to drive the medicine in a "special taxi" as a surgical procedure directly to the sick cells."

The research was led by Prof. Parr together with Dr. Nils Dams, a postdoctoral student from the Netherlands, and in collaboration with Dr. Srinivas Ramishti, Dr. Meir Goldschmidt and Dr. Nofer Viga, from Prof. Dan Parr's laboratory. Prof. Jason Darling and Prof. Alan Packard from Harvard University in the USA also participated in the study. The research was funded by the European Union, within the framework of the European Excellence Program (ERC).

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