Naama Barak
July 10, 2023

In a first, Israeli researchers managed to encode a toxin produced by bacteria into mRNA molecules and to deliver it directly to cancer cells, causing them to produce the toxin that went on to kill them.

The study, led by PhD student Yasmin Granot-Matok and Prof. Dan Peer from Tel Aviv University and recently published in Theranostics, showed that a single injection into the tumor bed in animal models with melanoma skin cancer led to the disappearance of 44 to 60 percent of cancer cells.

“Many bacteria secrete toxins,” Peer explains. “The most famous of these is probably the botulinum toxin injected in Botox treatments. Another classic treatment technique is chemotherapy, involving the delivery of small molecules through the bloodstream to effectively kill cancer cells. However, chemotherapy has a major downside: it is not selective, and also kills healthy cells.”

“Our idea was to deliver safe mRNA molecules encoded for a bacterial toxin directly to the cancer cells – inducing these cells to actually produce the toxic protein that would later kill them. It’s like placing a Trojan horse inside the cancer cell.”

The researchers encoded the genetic information of a toxic protein produced by bacteria of the pseudomonas family into mRNA molecules – similar to the way genetic information of Covid-19’s spike protein was encoded into mRNA molecules to create the vaccine.

In first, scientists induce cancer cells to kill themselves
Prof. Dan Peer. Photo courtesy of Tel Aviv University

Then, the mRNA molecules were packaged in lipid nanoparticles and coated with antibodies. The particles were then injected into animal models with melanoma.

“In our study, the cancer cell produced the toxic protein that eventually killed it,” Peer says. “Many anaerobic bacteria, especially those that live in the ground, secrete toxins, and most of these toxins can probably be used with our method.”

He said that delivering the bacteria directly to the target cells with nanoparticles is like a recipe.

“When the cancer cell reads the ‘recipe’ at the other end, it starts to produce the toxin as if it were the bacteria itself and this self-produced toxin eventually kills it.

“Thus, with a simple injection to the tumor bed, we can cause cancer cells to ‘commit suicide’ without damaging healthy cells. Moreover, cancer cells cannot develop resistance to our technology as often happens with chemotherapy, because we can always use a different natural toxin.”

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