In recent years, ribonucleic acid (RNA) has emerged as a powerful tool for the development of novel therapies. RNA is used to copy genetic information contained in our hereditary material, the deoxyribonucleic acid (DNA), and then serves as a template for building proteins, the building blocks of life. Delivery of RNA into cells remains a major challenge for the development of novel therapies across a broad range of diseases. Researchers at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden together with researchers from the global biopharmaceutical company AstraZeneca have investigated where and how mRNA is delivered inside the cell. They found that mRNA uses an unexpected entry door. Their results provide novel insights into the development of RNA therapeutics towards efficient delivery and lower dosages.
DNA (deoxyribonucleic acid) contains the genetic information required for the development and maintenance of life. This information is communicated by messenger ribonucleic acid (mRNA) to make proteins. mRNA-based therapeutics have the potential to address unmet needs for a wide variety of diseases, including cancer and cardiovascular disease. mRNA can be delivered to cells to trigger the production, degradation or modification of a target protein, something impossible with other approaches. A key challenge with this modality is being able to deliver the mRNA inside the cell so that it can be translated to make a protein. mRNA can be packed into lipid nanoparticles (LNPs)—small bubbles of fat—that protect the mRNA and shuttle it into cells. However, this process is not simple, because the mRNA has to pass the membrane before it can reach its site of action in the cell interior, the cytoplasm.
Researchers in the team of MPI-CBG director Marino Zerial are experts in visualizing the cellular entry routes of molecules in the cell, such as mRNA with high-resolution microscopes. They teamed up with scientists from AstraZeneca who provided the researchers with lipid nanoparticle prototypes that they had developed for therapeutic approaches to follow the mRNA inside the cell. The study is published in the Journal of Cell Biology.
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