The Pentagon’s research and technology arm is preparing to launch a new program that aims to fundamentally alter the role of human red blood cells through synthetic biology.
The Defense Advanced Research Projects Agency (DARPA) announced the forthcoming Smart-Red Blood Cells (Smart-RBC) initiative in a special notice released by its Biological Technologies Office on September 10, 2025.
According to the notice, the Smart-RBC program seeks to engineer red blood cells with embedded biological circuits capable of sensing, deciding, and acting on physiological signals. These engineered cells—referred to as “smart red blood cells” or SRBCs—are intended to enhance performance in austere environments and improve survival during trauma by supporting physiological regulation and clotting.
“The Smart-RBC program aims to engineer red blood cells to contain novel biological features that can safely and reliably modify human physiology,” the agency said. DARPA says the program will “revolutionize blood products” by embedding programmable functions into cells traditionally used only for oxygen delivery.
The SRBCs will feature synthetic biological circuits with three core functions: sensing biomarkers, making decisions, and releasing effector molecules that alter metabolic or physiological conditions. Initial applications will focus on performance support and enhanced hemostasis, with future capabilities potentially including thermal regulation, universal blood compatibility, and high-altitude adaptation.
DARPA has structured Smart-RBC as a 36-month effort, broken into two 18-month phases. In Phase I, teams will demonstrate that synthetic circuits can be integrated during stem cell differentiation and remain functional in mature, enucleated red blood cells. In Phase II, researchers will refine the systems, demonstrate performance, and complete a live capability demonstration.
The program is being led by Dr. Christopher Bettinger, the Technical Point of Contact within DARPA’s Biological Technologies Office. For new participants, DARPAConnect provides resources and onboarding guidance for those unfamiliar with the agency’s contracting processes.
While still in its early stages, the Smart-RBC initiative reflects the Pentagon’s growing investment in synthetic biology as a defense-enabling capability, aimed at improving survivability, endurance, and adaptability in increasingly hostile environments.