ARLINGTON, Va. – U.S. military researchers are asking industry to create smart red blood cells that enhance human performance under austere military conditions; support quick recovery; and improve the chances of survival during combat.
Officials of the U.S. Defense Advanced Research Projects Agency (DARPA), in Arlington, Va., issued a program solicitation (DARPA-PS-26-02) on Friday for the Smart Red Blood Cells (Smart-RBC) program.
This initiative seeks to enable human blood not only to carry oxygen, but also to sense extracellular biomarkers in the bloodstream; decide on the correct response based on these signals; and act by releasing effector molecules that can modify metabolism or other aspects of human physiology.
Medical applications eventually could include universal blood types, rapid acclimation to high altitudes, thermal regulation, and even on-demand therapeutic delivery for diseases using red blood cells as carriers.
Modified stem cells
The goal of the Smart Red Blood Cells project hinges on modifying stem cells such that mature red blood cells retain new programmable functions to enable these new human capabilities. It aims to engineer red blood cells to contain biological features that can safely, temporarily, and reliably alter human physiology.
Smart blood will be engineered to contain additional biological circuits consisting of three layers: sensing extracellular biomarkers; deciding next steps; and acting by creating effector molecules that can alter metabolism or physiology. This program does not include clinical trials or direct human testing.
Warfighters today must make the most of human performance and survivability in extreme conditions like cold, high altitude, jungle warfare, or amid bullets, shrapnel, airborne poisons, and biological agents.
Natural acclimation to physical exertion, extreme cold, or high altitudes offers reduced injury and can enhance performance, but requires weeks to years for a durable outcome. Currently available solutions are ineffective, slow, impractical, scale poorly, can produce dangerous side effects.
Tell me more about smart red blood cells ...
- Smart red blood cells are engineered to retain their original oxygen-carrying role, but are augmented with nanotechnology, genetics, or synthetic biology to serve as delivery systems, biosensors, or even therapeutic agents. They are loaded, coated, or modified to carry drugs inside or on their surfaces to release them gradually or in response to specific triggers like cancer, autoimmune disorders, or infections. They can involve detoxification agents; artificial oxygen carriers; biosensors; or gene delivery. Smart red blood cells are being explored for personalized medicine; cancer immunotherapy; long-term controlled drug release; bio-hybrid artificial blood; and autoimmune disease management.
Experts in the DARPA Biological Technologies Office are looking for solutions that are fast, offer feedback; are safe, are effective for as long as 120 days. Red blood cells comprise more than 80 percent of cells in the human body; circulate for as long as 120 days; and interact with every organ. Modified red blood cells also cannot transfer genetic material, and are stored and transported easily.
Engineered red blood cells should have sensors to detect at least two unique biomarkers; at least two logic gates to convert biomarker responses into an interpretation of physiological state; and offer a response that can amplify changes in biomarker signals by at least 100 times to create a physiological response to a potentially minute biological signal.
In addition, the biological circuit design also must address cell fitness and safety, and must be enucleated to minimize the risk of transferring modified genetic material to a prospective recipient.
Radiological and chemical weapons protection
Of interest are engineered red blood cells capable of self-renewal and replication; protection against radiation, biological, or chemical weapons; lead to development of artificial cells or synthetic cells.
Companies interested should submit abstracts no later than 12 Nov. 2025 to the DARPA BAA Tool online at https://baa.darpa.mil. Those submitting promising abstracts may be invited to give oral proposals in mid-January 2026.
Email questions or concerns to DARPA at [email protected]. More information is online at https://sam.gov/workspace/contract/opp/a0160217c997497c897c3320db9dcb7f/view.
