Soldiers on future battlefields could be protected against germ warfare agents by having blood transfusions with genetically modified cells that can neutralise deadly biological toxins, scientists have found.
Human red blood cells have been genetically engineered to produce protein antidotes and other antibody-based medicines that can be safely delivered to any part of the body, researchers said.
A study has shown that the technique works well when carried out on laboratory mice, and that modified human red blood cells stay circulating in the body for up to four months, giving transfusion patients long-term protection, they said.
Red blood cells normally carry oxygen from the lungs to the living tissues and are the most numerous of all the cells, accounting for about a quarter of the 100 trillion cells of the human body. They are deliberately small and flexible to allow them to flow through narrow capillaries.
They also lack their own chromosomes because the red cell nucleus is lost during development, making any genetic modification inherently safer as they cannot replicate to produce a cancerous tumour and are naturally removed from the bloodstream after four months.
“We wanted to create high-value red cells that do more than simply carry oxygen. Here we’ve laid out the technology to make mouse and human red blood cells in culture that can express what we want and potentially be used for therapeutic or diagnostic purposes,” said Harvey Lodish of the Whitehead Institute for Biomedical Research in Massachusetts.
A study published in the journal Proceedings of the National Academy of Sciences shows that it is possible to use human red blood cells as microscopic vehicles for carrying a cargo of genetically engineered proteins in the cell’s outer membrane that can be targeted against specific toxins.
The research was supported by the US Defence Research Projects Agency (Darpa), the scientific funding arm of the US military, which is interested in developing the technology for future treatments or vaccines against biological weapons, the researchers said.
“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 neutralise a toxin. The result would be long-lasting reserves of antitoxin antibodies,” said Hidde Ploegh, professor of biology at the Massachusetts Institute of Technology, one of the study’s senior authors.
The researchers made the genetic modifications to the precursor cells that develop into fully mature red blood cells. The technique could also be used to produce modified red cells engineered to remove bad cholesterol from the blood stream, to carry clot-busting proteins to treat strokes or deep-vein thrombosis or to deliver anti-inflammatory antibodies to alleviate chronic inflammation, the researchers said.
“Moreover, the established safety of blood transfusions inspires confidence that these engineered red blood cells indeed will find use in humans,” they said.