Researchers at Chalmers University of Technology in Sweden and collaborators created a technique to produce fluorescently labeled mRNA, which allows them to track their entry and distribution into cells. The use of these molecules could help scientists develop better ways to administer mRNA therapies to the body, potentially playing a vital role in the new wave of mRNA therapies, including vaccines.
MRNA therapies enjoy a prominent moment, as two of the most effective and coveted COVID-19 vaccines, produced by Pfizer / BioNTech and Moderna, use the technology. Once considered too fragile for therapeutic use, the COVID-19 pandemic has shown that mRNA is a force to be reckoned with, if used correctly. However, the technology has some drawbacks, especially for routine use in large populations, as it requires storage at very low temperatures, which makes expensive and impractical cold chain transport necessary.
The fragility of mRNA molecules also underscores their need for special nanoscale packaging so that they can reach target cells without being destroyed in the body. At present, this can be achieved by lipid vesicles that rock the fragile molecules until they are captured in the cells. However, researchers are still learning the best ways to package and deliver mRNA, and optimizing it is key to advancing technology. Currently, the delivery of mRNA to cells is somewhat inefficient and there is room for improvement.
Finding better methods to efficiently manage mRNA requires almost one way to track where the molecule travels. So far this has been very difficult. This latest technique from Chalmers University of Technology changes that. It is a fluorescent unit created by the researchers, which can replace a base called cytosine that is normally part of the mRNA, resulting in fluorescent mRNA strands. Fluorescently labeled molecules can be visualized through a microscope, allowing researchers to track their movement as cells take them and then distribute them within the cells themselves.
“The great advantage of this method is that we can now easily see where the mRNA delivered to the cell is and in which cells the protein is formed, without losing the natural ability to translate proteins from the cell. ‘RNA,’ said Elin Esbjörner, a researcher involved in the study.
Researchers hope the technique could help accelerate the development of a new wave of mRNA therapy. “Since our method can help solve one of the biggest problems of drug discovery and development, we see that this research can facilitate a paradigm shift from traditional drugs to RNA-based therapy,” said Marcus Wilhelmsson, a another researcher involved in the study.
Study a Journal of the American Chemical Society: Stealth fluorescence labeling for live mRNA image microscopy