RNA-based nanodrugs cause cancer cells to collapse

The breakthrough was achieved by the TAU research team led by Dan Peer from the Shmunis School of Biomedicine and Cancer Research. Peer is head of the precision nanomedicine laboratory, and TAU’s VP of R&D. The team is also led by Sushmita Chatterjee, who is a postdoctoral student in Peer’s lab, in collaboration with David Sprinzak of the Wise Faculty of Life Sciences and Ronen Zaidel-Bar of the Sackler Faculty of Medicine.

This study was funded by the Rivkin Foundation for Ovarian Cancer Research and the Shmunis Family Foundation. The results are published in a scientific journal Science Advances.

Silencing the protein for the first time

In the second phase of the study, the researchers tested the new CKAP5 silencer RNA drug in 20 types of cancer. Some cancer cells have been shown to be more sensitive than others to this procedure. Cancers displaying high genetic instability, which are usually highly resistant to chemotherapy, were found to be especially sensitive to the silencing of CKAP5.

“All cancer cells are genetically unstable,” Chatterjee said.

“Otherwise they would be healthy, not cancerous. However, there are varying degrees of genetic instability. We found that the more unstable the cancer cells, the more affected by CKAP5 damage. Our medicine pushes them to their limits, and basically destroys their structure. Our idea is to turn genetic instability into a threat to these cells, by using RNA to silence defective proteins. We demonstrated for the first time that CKAP5 can be used to kill cancer cells, and then observed a biological mechanism that causes cancer cells to collapse in the absence of protein.”

80% survival rate.

Armed with this insight, the researchers tested the new drug in animal models for ovarian cancer, achieving an 80% survival rate.

“We chose ovarian cancer because it targets well,” says Peer.

“Although very resistant to chemotherapy and immunotherapy, this type of cancer is very sensitive to CKAP5 silencing. It should be emphasized that the CKAP5 protein is a new target in the fight against cancer. Targeting cell division is not new, but using RNA to target proteins that make up the cell’s skeleton (cytoskeleton) – this is a new approach and a new target that must be further investigated.

“As researchers, we are involved in something like a dominoes game: we always look for the one piece in the cancer’s structure that is so important, that if we pull it out, the entire cell will collapse. CKAP5 is a domino piece, and we are working on more applications, this time in blood cancer.”