Dr. Dan Farr from the Department of Cell Research and Immunology is leading a new kind of research effort, with the aim of developing nanometric systems for transporting drugs, which will address a wide variety of diseases * The project, which encompasses 11 laboratories, will build a technological infrastructure, which will be available for commercialization and industrial application in five years * The work is already attracting a lot of interest among large pharmaceutical companies
"Our project was launched in 2012, and it is a focused research effort of a new type, the like of which has not been seen in Israel to date," says Dr. Parr. "Our goal is to establish a new technological infrastructure in the field of nanomedicine, which will be available for commercialization and industrial application in five years - a very short period in terms of scientific research. To this end, we have selected 11 research teams (of which eight are at Tel Aviv University), which are developing a wide spectrum of strategies in an advanced and fascinating field: tiny particles that carry drugs and imaging tools directly to their destination inside the human body. Our work is already attracting a lot of interest among large pharmaceutical companies."
The groups participating in the innovative project specialize in a variety of fields: chemical synthesis and polymers, antibody engineering, the immune system, use of particles of biological origin, cellular biology, imaging and cardiology. Their research deals with a wide range of diseases, mainly diseases involving a lack or excess of blood vessels, and diseases related to the immune system - such as various types of cancerous tumors and blood cancer, heart attacks, inflammatory processes and viral diseases that attack the immune system, including AIDS. The project receives significant support from the Israeli government, as part of the Israel National Nanotechnology Initiative (INNI) - an Israeli national initiative for nanotechnology, which aims to establish and promote nano centers in Israeli research institutions.
Dr. Parr's project partners at Tel Aviv University are: Prof. Ehud Gazit from the Faculty of Life Sciences, currently the Chief Scientist of the Ministry of Science, Prof. Itai Benhar and Prof. Ramona Margalit from the Faculty of Life Sciences, Prof. Doron Shabat and Prof. Moshe Portnoy from the School for Chemistry, Dr. Ronit Sachi-Painero from the School of Medicine and Prof. Yonatan Lior from the Faculty of Medicine and the Sheba Medical Center. In addition, partners in the project are Dr. Galia Blum from the Hadassah Ein Kerem School of Medicine, Dr. Ayelet David from the School of Medicine at Ben Gurion University and Prof. Shulamit Michaeli from Bar-Ilan University.
Drug transport to intestinal inflammations
Under the overall umbrella of the nanomedical project, Dr. Parr's research group focuses on the field of inflammatory bowel diseases, such as Crohn's and colitis. A multidisciplinary team of 18 researchers works in his laboratory - engineers, biotechnologists, physicists, biologists, chemists and veterinarians, and collaborates with many doctors and surgeons at the Sheba, Rabin and Tel Aviv (Ichilov) medical centers, and with the large center for intestinal diseases at the University of Calgary in Canada. "In the technological aspect, we are developing a strategy for transporting nanometer drugs and diagnostic tools to intestinal inflammations," explains Dr. Parr. "Our technology is based on particles with a nanometer diameter coated with antibodies. These antibodies recognize cells from the immune system found in the bloodstream, which are 'called' to the infected area of the body, and colonize it. Such cells can, according to our concept, be used as navigation systems, a kind of GPS, that will guide the nanometer particles directly to the target. Based on this approach, we even developed a method for diagnosing inflammatory bowel diseases, which is not invasive like the conventional techniques of colonoscopy and gastroscopy: we injected labeled nanometer particles into the bloodstream of laboratory animals, which settled on the cells of the immune system in the blood, 'traveled' with them to the diseased cells in the intestine, and marked them for imaging systems. In extended use, such particles can also carry and release drugs."
silence harmful genes
To fulfill a wide range of tasks, Dr. Parr and his team develop nanometric carriers in a variety of sizes and types, adapted to different diseases and tasks. All the carriers produced in the laboratory are based on combinations of biological substances - fats, sugars and proteins. Thus, for example, the researchers discovered that the lipids effectively trap drugs and imaging agents, while a coating of sugars prevents the particles from sticking to each other. The proteins are mainly antibodies and ligands, which attach to the surface of the particles, guide them to the target cells, and also help them penetrate into them.
But Dr. Farr is not satisfied with the development of smart drug carriers... "Many research groups all over the world are today developing nanometer drug carriers of different types and materials," he says. "The uniqueness of my lab is that we combine technology with biology. We have a dedicated biological team, which is also looking for the drugs themselves, and this combination gives our research a special power." The biologists in Dr. Parr's group develop drugs with an innovative approach in its own right: instead of killing the inflammatory cells, they seek to change them and turn them into anti-inflammatory cells. And another innovation: the researchers will examine tissue samples from patients using the technique of deep genetic sequencing, using extremely advanced equipment located at Tel Aviv University. They intend to locate the damaged genes, examine their RNA, and develop for them a new type of medicine called small interfering RNA (siRNA), which is able to silence the expression of the damaged genes. Dr. Parr's group is a world pioneer when it comes to manipulating immune system cells using siRNA molecules. In the future, the method will make it possible to match each patient with a personalized medicine, which is the most effective for him.
"The technologies and medicines we are developing can be used in the future to treat a wide variety of diseases: from intestinal inflammation, psoriasis and arthritis, to various types of blood cancer - leukemias, lymphomas and myelomas," predicts Dr. Parr. "For each disease and each patient it will be possible to build a different nanoparticle, specially adapted to the specific situation and needs. The results so far are very promising, and two start-up companies have already been established based on our work: Leuko Bioscience, located in Boston, USA, focuses on the field of blood cancers, and has already conducted initial clinical trials in humans, which were crowned with impressive success; and Quiet Therapeutics, an Israeli company that focuses on cancer, and is expected to reach the clinical trials stage within the next two years."
--------------------
Dr. Dan Farr is one of the pioneers in the use of the RNA molecule to manipulate leukocytes in various diseases related to the cells of the immune system. He was recruited in 2008 from Harvard University to Tel Aviv University in order to establish the laboratory for nanomedicine. He holds academic appointments at Harvard Medical School in Boston, Massachusetts and the Cancer Research Institute in Houston, Texas. Dr. Farr has published over 55 articles and book chapters, and serves as the editor of three important journals in the field of drug delivery systems, as a member of the scientific panel of five other journals, and as a scientific advisor to several start-up companies and large pharmaceutical companies in Israel and abroad. He submitted about 40 inventions for patent registration, some of which were approved and even commercialized in several companies, and founded two start-up companies: Leuko Bioscience located in Boston, and the Israeli Quiet Therapeutics.
