Stabilizing mRNA vaccines for delivery to cells

Messenger RNA-based vaccines and therapies can be delivered more easily due to a non-toxic polymer that protects the RNA and controls its release inside cells.

The advent of vaccines using messenger RNA (mRNA) to direct the synthesis of immunogenic proteins, the most popular of the vaccines against COVID-19, has allowed researchers to stabilize the mRNA and make it more efficient. It is encouraging to find better ways of providing.

A team at the University of Tokyo, together with colleagues in Japan and China, have now developed polymers that can interact with, stabilize and encapsulate mRNA, allowing highly efficient delivery into culture. can be given Human cells and living rat cells. they have published His work in the journal Advanced Materials Science and Technology.

“Beyond Vaccines for Infectious diseaseThe mRNA offers promising avenues for unprecedented treatments such as protein replacement therapy, gene editing and immunotherapies, says Horacio Cabral of the University of Tokyo team. is the most important.”

Researchers investigated ways to fine-tune their structure. Polymer The molecules allow them to interact with the mRNA to protect it. The biocompatible and non-toxic polymers were of a type called block copolymers, made from alternating segments of different chemical groups, in this case polyethylene glycol and polyglycerol.

But the key to achieving the proper interaction with mRNA was the attachment of specific positively charged amino acid groups to the long polymer backbone. The positive charge usually attracts the polymer to the negatively charged RNA, and selected amino acids were also able to interact with parts of the mRNA in a process called pi–pi (π–π) stacking. It involves interactions between electrons in a feature called pi bonds in interacting molecules stacked side by side in cyclic molecular rings.

“This is a highly customizable approach, which allows us to fine-tune the interaction of our polymer with mRNA,” says Cabral. As a result, the mRNA was stabilized very efficiently, overcoming a major drawback of instability found with alternative methods.

The polymer and mRNA self-assembled into spherical bundles—micelles—that efficiently delivered the mRNA cargo into cultured cells as well as into mouse cells after intramuscular injection. The mRNA was easily released into the cells to produce the proteins it encoded at high efficiency, and for much longer than alternative methods.

“This work was very difficult because of the delicate nature of mRNA, a very delicate molecule that needs protection from the outside. target cells But once inside, there’s an immediate exposure to the cell machinery,” says Cabral. He adds, “Our success is exciting because of its ability to transform mRNA delivery technology, precisely engineering , innovative release strategies, and overcoming significant hurdles to increase stability and efficacy. mRNA-Based Therapeutics.”