The ease with which mRNA-based drugs are taken up by cells in tissues is important for their therapeutic effect. Currently, a new detection method developed by researchers at Chalmers University of Technology in Sweden and AstraZeneca could lead to faster and better development of small droplets known as lipid nanoparticles.
“We have developed an automated process for monitoring and testing many different types of products. Lipid nanoparticles At the same time, we hope to streamline the development of new drugs, “said Michael Manson, a postdoctoral fellow at AstraZeneca R & D, who belongs to the research center FoRmulaEx and is the lead author of a recently published study. Nature Communications Biology..
Messenger RNA or mRNA is the code used by. cell Produces protein. When introduced as a drug or vaccine, cells interpret it as a series of instructions and use a unique system to produce the protein of interest.
mRNA-based technologies are being studied for their potential therapeutic potential. Chronic disease It may be tailored to a particular tissue in a variety of ways, including encoding therapeutic proteins. For example, it replaces the wrong protein or regulates the dysfunction of the cells that cause the disease.
However, this new technology presents some major challenges. First, cells must be “fooled” to take up mRNA molecules. One of the most advanced ways to do this is to pack the mRNA into small droplets called lipid nanoparticles.Is Nanoparticles Cells that enter large bubbles called endosomes transport their contents to the cell’s “lysosomes” or degradation stations. Lipid nanoparticles containing mRNA are endosomes at the right time to reach the cytoplasm of the cell. Must leave. It takes place before the endosomes reach the degradation station. Otherwise, the mRNA will be degraded and unable to function. This important step is called “endosome escape” and the exact timing is for mRNA-based medicines. The most important factor. Work.
The new study describes a method developed by researchers to monitor and analyze the movement of intracellular lipid nanoparticles using detectable fluorescent markers. In addition to being able to see if lipid particles are taken up by cells and the delivered mRNA can produce the encoded protein, researchers have also developed markers that accurately track when and where endosome escape occurred. .. How much.This marker is a fluorescent version protein It can be seen that galectin 9, mRNA accumulates when it escapes endosomes.
“Not only to see which lipid nanoparticles work best, but to understand what makes them work best and use that knowledge to develop and test new and improved nanoparticle formulations. Now we can do that, “says Michael Munson.
Erin Esbjornner, associate professor of chemical biology at Chalmers University of Technology and co-author of the study, explains the importance of delivering mRNA to target cells as accurately as possible.
“To reduce the risk of side effects such as the immune system caused by lipid particles, we want to use the lowest possible dose, especially for diseases that require long-term treatment. In such cases, the following are important: the moment the endosomes escape is optimally timed to get the mRNA out of the cytoplasm with maximum effect, “she says.
In addition to allowing researchers to evaluate large numbers of lipid particles at the same time, this new method looks at how efficiently lipid particles are delivered and how they function in different types of cells. It is also useful. This allows you to adjust drugs that target specific tissues such as the lungs and liver.
“Lipid nanoparticles have different functions in different cell types. For example, the appropriate formulation for delivery to hepatocytes can be very different in lung cells. Our new method is such. Understand why the differences exist and can help you leverage this knowledge. Make a new design. Lipid “Nanoparticles tailored to different targets in the body,” says Erin Esbjornner.
Michael J. Munson et al, High Throughput Galectin 9 Imaging Assay for Quantifying Nanoparticle Uptake, Endosomal Escape, Functional RNA Delivery, Communication biology (2021). DOI: 10.1038 / s42003-021-01728-8
Chalmers University of Technology
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