Future Soldiers to be Immune to Bio-Weapons

The next generation American soldiers may be immune to biological weapons.

Scientists have for the first time genetically modified red blood cells (RBC) to carry a range of valuable payloads ¡ª from drugs, to vaccines, to imaging agents ¡ª for delivery to specific sites throughout the body. RBCs 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.

The approach has captured the attention of the US military and it's Defence Advanced Research Projects Agency (Darpa), which is supporting the research in the interest of developing treatments or vaccines effective against biological weapons. "We wanted to create high-value red cells that do more than simply carry oxygen," says Whitehead founding member Harvey Lodish who collaborated with Whitehead member Hidde Ploegh in this pursuit. "Here we've laid out the technology to make mouse and human RBCs in culture that can express what we want and potentially be used for therapeutic or diagnostic purposes."

The scientists believe 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.

RBCs are an attractive vehicle for potential therapeutic applications for a variety of reasons, including their abundance ¡ª they are more numerous than any other cell type in the body ¡ª and their long lifespan (up to 120 days in circulation). Perhaps most importantly, during RBC production, the progenitor cells that eventually mature to become RBCs 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 tumour formation or other adverse effects. 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, scientists said.

Exploiting this characteristic, Lodish and his lab introduced genes coding for specific slightly modified normal red cell surface proteins into early-stage RBC progenitors. As the RBCs approach maturity and enucleate, the proteins remain on the cell surface, where they are modified by Ploegh's protein-labeling technique.

Referred to as "sortagging" the approach 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 four months, one could envision a scenario in which the cells are used to introduce antibodies that neutralize a toxin," says Ploegh. "The result would be long-lasting reserves of antitoxin antibodies".