Schematic illustration of TERRA structure and RIBOTAC-mediated mechanism of action. Credit: Advanced Science (2025). DOI: 10.1002/advs.202512715
Researchers have created a new type of drug molecule that can precisely destroy TERRA, an RNA molecule that helps certain cancer cells survive. Using advanced “RIBOTAC” technology, their compound finds TERRA inside cells and breaks it down without harming healthy molecules. This discovery could pave the way for a new generation of RNA-based cancer treatments, targeting the disease at its genetic roots rather than just its symptoms.
Scientists at the Hebrew University of Jerusalem developed the drug molecule. The research, published in Advanced Science, was led by Dr. Raphael I. Benhamou, Elias Khaskia, and Dipak Dahatonde from Hebrew University’s Faculty of Medicine. Their work focuses on a molecule called TERRA, which helps protect the ends of our chromosomes—the parts of our DNA that keep our cells healthy and stable.
When TERRA doesn’t work properly, it can cause problems with how cells age and divide. In some cancers, especially certain brain and bone cancers, cancer cells use TERRA to keep themselves alive and multiplying.
“We’ve created a tool that acts like a guided missile for bad RNA,” said Dr. Benhamou. “It can find TERRA inside cancer cells and make it disappear—without harming healthy parts of the cell.”
The team built a small molecule using a technology called RIBOTAC, short for Ribonuclease-Targeting Chimera. This molecule can recognize a unique shape that TERRA folds into—known as a G-quadruplex—and then call in a natural cell enzyme, RNase L, to cut the RNA apart.
This is the first time scientists have been able to destroy TERRA so precisely. The molecule only targets TERRA and leaves other, similar RNAs untouched.
When tested in cancer cell lines, including HeLa and U2OS cells (which represent a hard-to-treat type of cancer), the treatment reduced TERRA levels and slowed cancer growth.
The discovery could lead to a new kind of medicine that fights cancer by going after RNA molecules—not just proteins, which most drugs target today.
“This is a new way of thinking about medicine,” said Benhamou. “Instead of focusing only on proteins, we’re now learning how to target the RNA that controls them. That could open the door to treating diseases we once thought were impossible to reach.”
More information:
Elias Khaskia et al, RNA G‐Quadruplex RIBOTAC‐Mediated Targeted Degradation of lncRNA TERRA, Advanced Science (2025). DOI: 10.1002/advs.202512715
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Hebrew University of Jerusalem
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‘Guided missile’ drug molecule seeks out and destroys cancer’s genetic lifeline (2025, October 23)
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