Scientists from the International Institute of Molecular and Cell Biology in Warsaw (IIMCB) have published an exhilarating discovery. They announced one of the coolest new technological breakthroughs since they last discussed their neoteric celeb, mRNA. The laboratory of RNA Biology—ERA Chairs Group under Prof. Andrzej Dziembowski leads the research team. They investigated, in particular, how poly(A) tail metabolism affects mRNA stability and enhances the therapeutic potential of mRNA.
The unprecedented study, published in peer-reviewed journal Nature, used real-world data from the two most common anti-COVID-19 vaccines, Comirnaty and Spikevax. Both vaccines were essential tools in preventing the pandemic. As the researchers explain, mRNA is naturally unstable, which makes it ineffective. The IN-MOL-CELL infrastructure at IIMCB provided for the study. Researchers affiliated with the Ochota Campus, including the University of Warsaw and the Medical University of Warsaw, worked together on this project.
By bringing together experts in mRNA discovery and development, the research will directly address the mRNA stability hurdles. It’s opened the door to incredible new developments in mRNA-based medicines.
Research Insights on mRNA Stability
This work reveals a key new picture of the poly(A) tail. This critical aspect of mRNA has a huge impact on the stability and duration of action of mRNA. Professor Dziembowski emphasized the importance of this discovery:
“mRNA vaccines played a key role in controlling the spread of the pandemic. However, mRNA itself is an exceptionally unstable molecule. This does not affect the safety of the therapy but limits its effectiveness—for example, by shortening the duration of action. A particularly important role in mRNA stability is played by its so-called poly(A) tail. In our research, we examined these limitations.” – Prof. Andrzej Dziembowski
Dr. Paweł Krawczyk, a member of Dziembowski’s team responsible for computational methods in the study, noted their innovative approach:
“We created specialized software to analyze sequencing data from therapeutic mRNA molecules, focusing on poly(A) tail metabolism.” – Dr. Paweł Krawczyk
The researchers had already noted that during vaccination, the poly(A) tail experiences many changes. Dr. Seweryn Mroczek pointed out their initial curiosity regarding these changes:
“We wanted to understand how poly(A) tails change during the vaccine’s action.” – Dr. Seweryn Mroczek
That first question led us to a prolific understanding of a special type of immune cell called macrophages. In particular, it revealed what these cells do with mRNA inside vaccines.
Key Findings on Macrophage Interaction
Their research demonstrated that TENT5A—one of the proteins that poly(A) tail—which was required for effective vaccines. This lack thereof has huge detrimental impacts on vaccine efficacy. Dr. Mroczek emphasized the significance of their findings:
“During the course of the study, we demonstrated that the absence of TENT5A in macrophages reduces vaccine efficacy.” – Dr. Seweryn Mroczek
Preliminary data showed that poly(A) tail extensions are a key feature of macrophages in response to vaccination. These imperfections can be corrected by adding extensions to mRNA, which increase its stability, letting it work longer inside cells.
These discoveries shed light on how mRNA operates. They underscore promising routes to optimize existing mRNA-based treatments.
“Until now, it was assumed that the poly(A) tail of mRNA therapeutics could only be shortened. Extending it is like flipping over an hourglass—it ‘buys’ extra time, allowing the mRNA to function significantly longer in cells.” – Dr. Paweł Krawczyk
As an example, the 2006 publication’s contributions have far-reaching implications outside of basic science. They set the stage for future breakthroughs in mRNA therapeutics. Professor Dziembowski stated:
Implications for Future Research
With a deeper understanding of poly(A) tails and greater control over their manipulation, researchers hope to develop better disease therapies. The collaboration between IIMCB and other research entities has proven fruitful and may lead to breakthroughs that enhance patient outcomes.
“In future studies within the Virtual Research Institute, we plan to use our discoveries to develop improved mRNA-based medicines.” – Prof. Andrzej Dziembowski
This study’s rigorous approach to answering the study question provides strong support for its credibility. It underwent a thorough peer-review process and adhered to Science X’s editorial standards, ensuring that findings are reliable and accurately represented.
The rigorous nature of this study also underscores its credibility. It underwent a thorough peer-review process and adhered to Science X’s editorial standards, ensuring that findings are reliable and accurately represented.