Researchers from the Whitehead Institute have developed a method for engineering red blood cells to act as carriers for a wide range of valuable cargo. It is hoped that this technique could eventually be employed as a tool to deliver various agents throughout the body, from antibodies to drugs and diagnostic imaging probes. The study has been published in PNAS.
Red blood cells, or erythrocytes, are an attractive candidate as a cargo vessel for numerous reasons. They have a long lifespan in circulation, around 120 days, and are found in copious amounts throughout the body. Furthermore, red blood cells do not contain any genetic material as the progenitor cells that mature into these cells eject their nuclei. This therefore alleviates the risk of transplanted cells going haywire and causing tumors in recipients which is a common concern when transplanting modified cells.
In order to generate these carriers, the researchers genetically modified progenitor cells by introducing genes that encode a specific set of modifiable proteins that localize to the surface of the cell. When these engineered cells then mature into erythrocytes, the genetic material is ousted but the surface proteins remain on the plasma membrane.
The researchers then adopted a protein-labeling technique known as sortagging to attach various molecules to the cell. This method exploits a bacterial enzyme known as sortase A in order to covalently link the molecule of choice to the surface protein without damaging the cell.
“Because the modified human red blood cells can circulate in the body for up to four months, one could envision a scenario in which the cells are used to introduce antibodies that neutralize a toxin,” said co-lead researcher Hidde Ploegh in a news-release. “The result would be long-lasting reserves of antitoxin antibodies.”
The researchers demonstrated proof of principle in the laboratory using both mouse and human cells and hope that with further work, they may be able to translate this into a valid method for the delivery of diagnostic or therapeutic agents.
According to co-lead researcher Harvey Lodish, the potential applications for this technique are vast. For example, they could eventually be used to deliver anti-clotting agents as a way to treat ischemic stroke or deep vein thrombosis, or anti-inflammatory antibodies to treat chronic inflammation. However, it is early days yet and while the modified cells remained in the bloodstream of mice for up to 28 days, much more needs to be done before these cells can approach humans.
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