Engineered red blood cells could carry drugs, vaccines

Scientists supported by the Defense Advanced Research Projects Agency recently modified red blood cells to carry payloads like drugs and vaccines, according to research published in the Proceedings of the National Academy of Sciences.

The researchers from the Whitehead Institute for Biomedical Research genetically and enzymatically modified the red blood cells (RBCs) to carry a variety of cargo, including drugs, vaccines and imaging agents, for delivery to certain sites in the body. DARPA is supporting the research to develop potential treatments or vaccines that are effective against biological weapons.

"We wanted to create high-value red cells that do more than simply carry oxygen," Harvey Lodish, the founding member of Whitehead Institute, said. "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."

RBCs are more numerous than any cell type in the body, have a long lifespan and lack any genetic material or signs of earlier genetic manipulation that could lead to tumor formation or other adverse effects.

Lodish and fellow Whitehead member Hidde Ploegh introduced genes to code for modified normal red cell surface proteins into early-stage RBC progenitors. When the RBCs approach maturity and enucleate, the proteins remain on the cell surface where they are monitored by a protein labeling technique called sortagging.

Sortagging uses the bacterial enzyme sortase A to establish a chemical bond between a surface protein and a substance of choice, whether it be an antibody, a therapeutic or an imaging agent. The modifications do not harm the cells in any way.

"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," Ploegh said. "The result would be long-lasting reserves of antitoxin antibodies."

Lodish said the technique could lead to modified RBCs to remove bad cholesterol, treat ischemic strokes or alleviate chronic inflammation.