Researchers at Tel Aviv University have, for the first time ever, encoded a bacterial toxin into messenger RNA (mRNA) molecules and delivered these molecules directly to cancer cells, causing the cells to produce the toxin and ultimately killing them with a 50% success rate.
Yasmin Granot-Matok, a Ph.D. student, and Prof. Dan Peer, a pioneer in the development of RNA therapeutics and Head of the Nanomedicine Laboratory at the Shmunis School of Biomedicine and Cancer Research who also serves as TAU’s Vice President of Research and Development, led the groundbreaking study, which was published in Theranostics.
Prof. Peer provides the following explanation: The botulinum toxin that is injected during Botox treatments is probably the most well-known of these. Chemotherapy, which involves the delivery of small molecules through the bloodstream to kill cancer cells, is another well-known treatment option. However, chemotherapy has a significant drawback: It also kills healthy cells and is not selective. Our idea was to deliver safe mRNA molecules that were encoded for a bacterial toxin directly to the cancer cells. This would cause the cancer cells to produce the toxic protein that would kill them later. It’s similar to inserting a Trojan horse into a cancer cell.
“The cancer cell in our study produced the toxic protein that eventually killed it. We employed pseudomonas bacteria and melanoma cancer for the sake of convenience. Many anaerobic bacteria, particularly those found in the soil, release toxins, and the majority of these toxins are likely to be used using our approach. This is our’recipe,’ and we understand how to deliver it directly to the target cells using nanoparticles.”
Prof. Dan Peer, a pioneer in the development of RNA therapeutics.
To begin, the team encoded the toxic protein’s genetic information into mRNA molecules, similar to how the vaccine’s genetic information was encoded into mRNA molecules to make COVID-19’s spike protein.
The mRNA molecules were then encased in antibody-coated lipid nanoparticles developed in Prof. Peer’s lab to guarantee that the cancer cells they were intended to kill would receive the toxin’s instructions. The particles were injected into the melanoma skin cancer tumors of animal models. A single injection killed between 44% and 60% of the cancer cells.
Prof. Peer claims, “In our study, the cancer cell produced the toxic protein that eventually killed it.” We used the melanoma cancer and the pseudomonas bacteria, but this was just for convenience. The majority of the toxins produced by many anaerobic bacteria, particularly those that reside underground, can probably be utilized with our method. With our nanoparticles, we are able to deliver this “recipe” directly to the target cells.”
“The cancer cell starts producing the toxin as if it were the bacteria itself when it reads the recipe at the other end. This self-produced toxin eventually kills the cancer cell. Therefore, we can “commit suicide” without harming healthy cells by simply injecting into the tumor bed. Furthermore, we can always use a different natural toxin, so cancer cells cannot develop resistance to our technology like they do to chemotherapy.
More information: Yasmin Granot-Matok et al, Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors, Theranostics (2023). DOI: 10.7150/thno.82228
