Modified mRNA raises hope for safe and effective cancer drugs

February 14, 2016

It was due to their own chemical methods that the scientists from FUW have developed and investigated many artificial varieties of cap structure. Several groups of structures discovered in this manner have been submitted for a patent. Compounds in which an oxygen atom in the triphosphate bridge was substituted with a sulphur atom have proven to be particularly significant. "An average mRNA particle consists of eighty thousand atoms; we have changed only one. This slight modification has had some fascinating consequences," says Joanna Kowalska, PhD (FUW). Conducted by the group led by Prof. Roberta E. Rhoads (LSU), investigations of mRNA chains with a new endpoint have proven it is possible to achieve a threefold increase in the lifetime of mRNA in a cell and a fivefold increase in its productivity in protein production. Tests on mice, in turn, conducted in Mainz by the BioNTech company and the local university, have revealed that the mice's immune system response to the given protein was three times stronger than in the case of unmodified mRNA. "These are very exciting results. The improvement obtained by using the modified cap analogs as developed at the University of Warsaw might turn out to be the key for an efficacious RNA-based immunotherapy," states Ugur Sahin, CEO of BioNTech and Professor at the University Medical Center Mainz.

The invention of the Polish scientists is paving the way for using the translation mechanism occurring in the cytoplasm for medical purposes. The new-generation drugs will have many merits. The compound introduced into the organism does not have to penetrate the cell nucleus. The lack of interference in the genome eliminates the risk of mutation, and the limited lifetime of mRNA chains allows a physician to trigger a particular response of the organism only when necessary. What is more, the defense reaction of the organism to foreign mRNA is considerably more specific than in the case of DNA. "Our methods for modifying and developing cap structures work perfectly well in test tubes, which is essential for anyone setting his or her mind on the industrial production of drugs," observes Jacek Jemielity, PhD.

The licence for the use of the methods related to the modifications of mRNA endpoints has just been bought by the German company BioNTech from Mainz. Already this year, they intend to begin the first phase of the clinical trials of a new anti-cancer drug, in which the therapeutic sequences of nucleotides in the mRNA end with a cap modified according to the guidelines laid down by the Polish scientists. The drug will be injected into the lymph nodes. There it will reach the dendritic cells, where the key elements of our immune system, T lymphocytes, will be able to specialize in destroying a protein singled out by the scientists.

Source: BioNTech