An LNP is located on a long endosomal tubule and is likely to be an instance of a mRNA escape. Marino Zerial is a member of the MPI-CBG.
Ribonucleic acid has become a powerful tool for the development of novel therapies. Our hereditary material, the deoxyribonucleic acid (DNA), contains genetic information that can be copied with the help of the ribonucleic acid, orRNA. Delivery of RNA into cells is a major challenge for the development of novel therapies. Researchers from the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden and from the global pharmaceutical company AstraZeneca have been studying the delivery of messenger RNA inside the cell. They found that the door is unexpected. Their results show how to develop efficient delivery and lower dosages of RNA.
The genetic information required for the development and maintenance of life is contained in the DNA. This information is communicated by messenger ribonucleic acid. The challenge with this method is that it can't be delivered inside the cell so that it can be translated. This process is not easy because the messenger RNA has to pass the cell's outer shell before it can reach the inside of the cell.
The researchers in the team of MPI-CBG are experts in visualization of the cellular entry routes of molecules. They collaborated with scientists from AstraZeneca who gave the researchers prototypes of the lipid nanoparticle prototypes that they had developed for therapeutic approaches to follow the mRNA inside the cell. The study was published in a journal.
To be delivered, the mRNA must travel a long way. It needs to get into the cell first before it gets out of the LNP bubble. The LNPs arrive at the cell surface. They are taken up into the endosomes. At this point, the cells are surrounded by two barriers, the fatty bubble and the endosome wall. The challenge for the mRNA is to escape both barriers to reach the cytoplasm where it serves as a template to make proteins. Only a tiny fraction of the molecule can escape into the nucleus.
The LNPs are first transported to endosomes. Logistic centers distribute cargo to various destinations in the cell. They either recycle the molecule to the cell surface or degrade it. People thought that the mRNA escapes from late endosomes.
The first time we could see the LNP in the endosomes was with single molecule microscopy. The escape of the mRNA happened in the tubules of the recycling endosomes, which are mildly acidic.
The results show that sending the LNP-mRNA to late endosomes increases cell toxicity. Understanding the mechanism of escape from endosomes is aided by these findings.
The low endosomal escape efficiency of the LNP delivery system necessitates high doses. Knowing where the mRNA goes and how it can escape the endosomes allows us to develop better vehicles for more efficient delivery. We can improve the delivery system so that it can be used for therapeutic purposes.
Prasath Paramasivam and his team visualized the endosomal escape of the mRNA from the endosomal recycling tubules. There is a book titled "JBC.202110137."
The Journal of Cell Biology has information.
If you can, please tell me about how mRNA therapies are delivered into cells.
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