Unlock the power of stereochemistry to improve the delivery of medicines to mRNA

A team from the Max-Planck-Assitut Für Kohlenforschung. Furthermore, Hokkaido University and Osaka University has discovered that subtle differences in the molecular structure can have a major impact on the performance of mRNA drugs. However, Their results. However, published in the Journal de l’American Chemical SocietyOpen the door to the development of safer and more effective vaccines and therapies.

To provide therapeutic nucleic acids such as mRNA in cells. Meanwhile, scientists are counting on lipid nanoparticles (LNP), tiny fat -based carriers that protect a fragile genetic material, which allows it to survive in the body and reach target cells. Similarly, A key component of these LNPs is ionizable lipids. Similarly, which help the mRNA to enter the cells, then to release it effectively. Meanwhile, One of these lipids. Consequently, ALC-315, was used unlock power stereochemistry improve delivery in particular in the Pfizer / Biontech COVVI-19 vaccine, a medical breakthrough that played an essential role in controlling the world pandemic.

The neglected impact of stereochemistry

Although the vaccine is safe. very effective, a surprising detail has remained largely unnoticed: ALC-315 is used as a mixture of three stereoisomers-molecules which have the same chemical formula but differ in their three-dimensional arrangement, a bit like left and right hands. This distinction is not trivial. It is well known that stereoisomers can behave very differently in biological systems. affecting how drugs are absorbed, distributed and metabolized. Until now. the three isomers of ALC-315 ((S, s), (R, R), et mesohad never been studied individually in the context of LNP’s performance. In their revolutionary study, Dr. Chandra Kanta of Max-Planck-Assitut für Kohlenforschung and his colleagues synthesized and tested each pure stereoisomer for the first time.

We demonstrate that stereochemistry directly affects LNP unlock power stereochemistry improve delivery efficiency and safety. In particular. we found that the (S, s) -Form provides mRNA just as effectively as the standard mixture, but with significantly reduced toxicity. “”

Dr Chandra Kanta de, Max Planck Institute for Coal Research

Dr. Masumi Tsuda of Hokkaido University in Japan. who carried out the biological analysis of the ALC-315 isomers with Professor Shinya Tanaka, said: “We would be delighted if these research results could contribute to the development of safer vaccines. »»

These results are very relevant because LNP technology is developing rapidly beyond COVVI-19 vaccines. with applications ranging from gene therapy to personalized cancer vaccines. While the field grows towards the next generation of therapies based on mRNA. the need for precise and optimized components is becoming more and more important. The study opens the way to improved LNP formulations. offering the potential of a safer and more efficient mRNA unlock power stereochemistry improve delivery delivery in broad spectrum of future therapies.

The work was supported by the Max Planck Society. the German Research Foundation (DFG), the European Research Council (ERC), the Japan Society for the Promotion of Science and the Japan Agency for Medical Research and Development (Amed).