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Researchers say they’ve modified red blood cells (RBCs) to carry a range of payloads—from drugs to vaccines to imaging agents.
“We wanted to create high-value red cells that do more than simply carry oxygen,” said study author Harvey Lodish, PhD, of the Whitehead Institute in Cambridge, Massachusetts.
“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.”
Dr Lodish and his colleagues detailed the technology in Proceedings of the National Academy of Sciences.
The team noted that RBCs are an attractive vehicle for a variety of reasons, including their abundance and their long lifespan.
Perhaps most importantly, during RBC production, progenitor cells jettison their nuclei and all DNA therein. Without a nucleus, a mature RBC lacks any genetic material or any signs of earlier genetic manipulation that could result in tumor formation or other adverse effects.
Exploiting this characteristic, Dr Lodish and his colleagues introduced into early stage RBC progenitors genes coding for specific, slightly modified, normal red cell surface proteins.
As the RBCs approach maturity and enucleate, the proteins remain on the cell surface, where they are modified by a protein-labeling technique known as sortagging.
The technique relies on the bacterial enzyme sortase A to establish a strong chemical bond between the surface protein and a substance of choice, be it a small-molecule therapeutic or an antibody capable of binding a toxin. The modifications leave the cells and their surfaces unharmed.
“Because the modified human red blood cells can circulate in the body for up to 4 months, one could envision a scenario in which the cells are used to introduce antibodies that neutralize a toxin,” said Hidde L. Ploegh, PhD, also of the Whitehead Institute. “The result would be long-lasting reserves of antitoxin antibodies.”
The approach has captured the attention of the US military and its Defense Advanced Research Projects Agency, which is supporting the research in the interest of developing treatments or vaccines effective against biological weapons.
Dr Lodish believes the applications are potentially vast and may include RBCs modified to bind and remove bad cholesterol from the bloodstream, carry clot-busting proteins to treat ischemic strokes or deep-vein thrombosis, or deliver anti-inflammatory antibodies to alleviate chronic inflammation.
Dr Ploegh said there is evidence to suggest that modified RBCs could be used to suppress the unwanted immune response that often accompanies treatment with protein-based therapies.
He is exploring whether these RBCs could be used to prime the immune system to allow patients to better tolerate treatment with such therapies. 
Researchers say they’ve modified red blood cells (RBCs) to carry a range of payloads—from drugs to vaccines to imaging agents.
“We wanted to create high-value red cells that do more than simply carry oxygen,” said study author Harvey Lodish, PhD, of the Whitehead Institute in Cambridge, Massachusetts.
“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.”
Dr Lodish and his colleagues detailed the technology in Proceedings of the National Academy of Sciences.
The team noted that RBCs are an attractive vehicle for a variety of reasons, including their abundance and their long lifespan.
Perhaps most importantly, during RBC production, progenitor cells jettison their nuclei and all DNA therein. Without a nucleus, a mature RBC lacks any genetic material or any signs of earlier genetic manipulation that could result in tumor formation or other adverse effects.
Exploiting this characteristic, Dr Lodish and his colleagues introduced into early stage RBC progenitors genes coding for specific, slightly modified, normal red cell surface proteins.
As the RBCs approach maturity and enucleate, the proteins remain on the cell surface, where they are modified by a protein-labeling technique known as sortagging.
The technique relies on the bacterial enzyme sortase A to establish a strong chemical bond between the surface protein and a substance of choice, be it a small-molecule therapeutic or an antibody capable of binding a toxin. The modifications leave the cells and their surfaces unharmed.
“Because the modified human red blood cells can circulate in the body for up to 4 months, one could envision a scenario in which the cells are used to introduce antibodies that neutralize a toxin,” said Hidde L. Ploegh, PhD, also of the Whitehead Institute. “The result would be long-lasting reserves of antitoxin antibodies.”
The approach has captured the attention of the US military and its Defense Advanced Research Projects Agency, which is supporting the research in the interest of developing treatments or vaccines effective against biological weapons.
Dr Lodish believes the applications are potentially vast and may include RBCs modified to bind and remove bad cholesterol from the bloodstream, carry clot-busting proteins to treat ischemic strokes or deep-vein thrombosis, or deliver anti-inflammatory antibodies to alleviate chronic inflammation.
Dr Ploegh said there is evidence to suggest that modified RBCs could be used to suppress the unwanted immune response that often accompanies treatment with protein-based therapies.
He is exploring whether these RBCs could be used to prime the immune system to allow patients to better tolerate treatment with such therapies.
Researchers say they’ve modified red blood cells (RBCs) to carry a range of payloads—from drugs to vaccines to imaging agents.
“We wanted to create high-value red cells that do more than simply carry oxygen,” said study author Harvey Lodish, PhD, of the Whitehead Institute in Cambridge, Massachusetts.
“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.”
Dr Lodish and his colleagues detailed the technology in Proceedings of the National Academy of Sciences.
The team noted that RBCs are an attractive vehicle for a variety of reasons, including their abundance and their long lifespan.
Perhaps most importantly, during RBC production, progenitor cells jettison their nuclei and all DNA therein. Without a nucleus, a mature RBC lacks any genetic material or any signs of earlier genetic manipulation that could result in tumor formation or other adverse effects.
Exploiting this characteristic, Dr Lodish and his colleagues introduced into early stage RBC progenitors genes coding for specific, slightly modified, normal red cell surface proteins.
As the RBCs approach maturity and enucleate, the proteins remain on the cell surface, where they are modified by a protein-labeling technique known as sortagging.
The technique relies on the bacterial enzyme sortase A to establish a strong chemical bond between the surface protein and a substance of choice, be it a small-molecule therapeutic or an antibody capable of binding a toxin. The modifications leave the cells and their surfaces unharmed.
“Because the modified human red blood cells can circulate in the body for up to 4 months, one could envision a scenario in which the cells are used to introduce antibodies that neutralize a toxin,” said Hidde L. Ploegh, PhD, also of the Whitehead Institute. “The result would be long-lasting reserves of antitoxin antibodies.”
The approach has captured the attention of the US military and its Defense Advanced Research Projects Agency, which is supporting the research in the interest of developing treatments or vaccines effective against biological weapons.
Dr Lodish believes the applications are potentially vast and may include RBCs modified to bind and remove bad cholesterol from the bloodstream, carry clot-busting proteins to treat ischemic strokes or deep-vein thrombosis, or deliver anti-inflammatory antibodies to alleviate chronic inflammation.
Dr Ploegh said there is evidence to suggest that modified RBCs could be used to suppress the unwanted immune response that often accompanies treatment with protein-based therapies.
He is exploring whether these RBCs could be used to prime the immune system to allow patients to better tolerate treatment with such therapies.