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Hebrew University Researchers Create Decoys that Block RNA-Binding Proteins from Spreading Cancer

Scientist Get Sly, Use Deception to Fight Cancer

QUOTE – And he replied, ‘I will go out and be a lying spirit in the mouth of all his Neviim.’ Then He said, ‘You will entice and you will prevail. Go out and do it.’ So Hashem has put a lying spirit in the mouth of all these Neviim of yours; for Hashem has decreed disaster upon you.” (1 Kings 22: 22-23)

Hebrew University’s Prof. Rotem Karni and Polina Cohen-Denichenko.Hebrew University’s Prof. Rotem Karni and Polina Cohen-Denichenko.

To combat cancer, an arch-enemy that kills millions of people around the world (and some 600,000 in the US alone), researchers sometimes revert to using trickery.

In recent years, it’s become clear that proteins that bind to RNA – ribonucleic acid, a molecule essential in various biological roles in coding, decoding, regulation and expression of genes – play a major role in cancer growth. These proteins, active in all cells but especially in cancer cells, bind to RNA molecules and accelerate cancer cell growth. Unfortunately, no cancer treatment has targeted these proteins – until now.

In an article titled “Specific inhibition of splicing factor activity by decoy RNA oligonucleotides” in the new issue of the prestigious journal Nature Communications, Prof. Rotem Karni and his team at the Hebrew University of Jerusalem present a new technology to fight cancer. They designed decoy molecules that trick RNA-binding proteins into binding with them. Once attached, these RNA-binding proteins are no longer able to bind with the natural RNA molecules in cancer cells, and they lose their cancer-promoting activity. These “sterile” RNA molecule decoys are called oligonucleotides.

“Our technology is a new approach in the war on cancer. By understanding the biological function of RNA-binding proteins, we successfully designed decoy molecules that inhibit these proteins and move us ever closer to creating an anti-cancer drug,” explained Karni.

Oligonucleotide, the RNA-binding decoy molecule.Oligonucleotide, the RNA-binding decoy molecule.

He and his Hebrew University Institute for Medical Research-Israel Canada (IMRIC) team, led by doctoral student Polina Cohen-Denichenko, developed several decoy molecules that inhibit the RNA-binding proteins that speed-up the growth of brain and breast cancer. To test the decoys, they treated brain cancer cells with decoy molecules. When the cells were then injected into healthy mice, the cancer cells did not replicate and, soon after, the tumors died off.

Although this study tested the efficacy of decoy molecules on breast and brain cancer cells, Karni explained that his technology enables scientists to tailor-make decoys for other types of cancer, thereby speeding up and improving treatment for cancer patients. “We still need to examine the toxicity of the decoy molecules and to test their efficacy on animals before we can move on to humans,” cautioned Karni. “However, I’m optimistic, given that we’ve already succeeded at creating decoy oligonucleotides that inhibit RNA binding proteins in other kinds of cancers.”

Karni recalls that his interest in science began when he was a small child in Kibbutz Ramat Hashofet in the north of Israel. “I used to catch reptiles and insects just so I could learn about them. My curiosity turned into ambitions of becoming a zoologist. I had dreams of studying animals in the South American rainforests.”

He decided to study biology at the Hebrew University and “fell in love with genetics and biochemistry. I specifically wanted to understand why and how cancer develops and progresses, affecting the lives of so many people around the world.” He spent five years on postdoctoral work at Cold Spring Harbor Laboratory in New York.

“Today, in my lab at IMRIC we are interested in how the process of alternative RNA splicing (a fundamental step of gene expression) is deregulated in cancer and other diseases, and how the proteins that control this process (called splicing factors) contribute to cancer development, tumor progression and the metastatic process.

To date, a patent describing this technology has been registered in the US and Europe by Yissum, the Hebrew University’s research and development company.