As red blood cells zip through the vessels, they provide oxygen to almost every nook and cranny of your body. But oxygen is not anything they can tote around. By orchestrating the red blood cells to have 'sticky' proteins on their surface, a team of researchers gave the cells the ability to transport anything from drugs to treat immune disorders or cancer to radioactive molecules used in the imaging of blood vessels.
"This is really a great idea, and a very new approach," said biochemist Vladimir Muzykantov of the University of Pennsylvania, who was not involved in the new work.
red blood cells represent a quarter of all human cells in the body and survive for an average of 4 months. Their ubiquity and durability makes it an ideal vehicle to transport therapeutic throughout the body, said Hidde Ploegh immunologist at the Massachusetts Institute of Technology in Cambridge. Previously, researchers have loaded red blood cells with drugs by pushing the molecules through the cell membrane in its interior, but the process weakens the cell, and the molecules are released when the cell reaches its final destination.
Ploegh and colleagues wanted instead of attaching molecules outside the red blood cells. Because red blood cells are not nuclei and therefore lack of genetic material that can be modified to make new proteins, the researchers turned to erythroblasts, the precursors of red blood cells that still contain DNA. Scientists added to erythroblasts modified versions of the genes are known to code for proteins present on the surface of red blood cells. The sequences of the introduced genes, however, had changes so that the erythroblasts produce surface proteins with an additional marker that is recognized by a protein called sortase.
These modified proteins remained erythroblasts matured in red blood cells. When the researchers added sortase mixtures of mature cells, the protein cut off the ends of all proteins, the researchers genetically modified, leaving teams of "sticky" trailers for freight. Any molecule with a label corresponding sortase would then bind to the surface protein of the red blood cell. To show that the coupling could work, team Ploegh attaches the vitamin biotin to red blood cells and infused into mice. The cells of biotin-toting survived for at least 28 days outstanding and do not harm the mice, they report online today in the Proceedings of the National Academy of Sciences .
Ploegh considering the technical being used to create a new type of personalized therapy in the cells of the future of your own could be isolated, used to create stem cells that differentiate into erythroblasts, genetically modified to carry a molecule and injected back into your body. Any molecule that has spread through the circulatory system could be the cargo. When the cells have matured into new red blood cells, they will have lost their DNA, eliminating the risk of changes in progress or dissemination of genetic material. "Payloads that you can install are unlimited," says Ploegh. "But many of the applications are still, for the moment hypothetical."
Muzykantov, who developed other approaches to the use red blood cells as molecular vehicles, said the importance of the new method "beyond just drug delivery. "It could be used to track the red blood cells to diagnose blood diseases, the spread of imaging agents through the body to visualize atherosclerotic plaques or blocked arteries, or counteract the immune system before transplantation by blocking antibodies that enter the bloodstream.
"But there are many issues to be addressed in animal models," he added. "I would love to see a real demonstration that a drug binds to a red blood cell using this approach always works. "
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