CaliToday (13/9/2025): The Pentagon's high-tech research and technology arm is embarking on an ambitious new program to fundamentally transform the role of human red blood cells using synthetic biology, aiming to create "smart blood" that can enhance soldier performance and survival on the battlefield.
The Defense Advanced Research Projects Agency (DARPA) officially announced the forthcoming Smart-Red Blood Cells (Smart-RBC) initiative in a special notice released by its Biological Technologies Office on September 10, 2025. The program seeks to engineer red blood cells with embedded biological circuits capable of sensing physiological cues, making decisions, and executing therapeutic actions.
These engineered cells, dubbed "smart red blood cells" or SRBCs, are intended to boost resilience in extreme environments and improve survivability after traumatic injury by actively assisting in physiological regulation and blood clotting.
"The Smart-RBC program aims to engineer red blood cells containing novel biological features that can safely and reliably modify human physiology," the agency stated in its announcement. DARPA elaborated that the initiative will "revolutionize blood products" by programming new functions into cells that are naturally limited to oxygen delivery.
From Oxygen Carriers to On-Demand Medics
The core of the Smart-RBC concept lies in equipping these cells with synthetic biological circuits designed for three primary functions:
Sensing: Detecting specific biomarkers and physiological signals within the body.
Decision-making: Processing the sensory input to determine if a specific condition is met.
Actuating: Releasing therapeutic molecules or effectors to alter metabolic or physiological conditions in response.
Initial applications will focus on performance enhancement and improving hemostasis (the process to stop bleeding). However, DARPA envisions a future where SRBCs could offer a range of capabilities, including thermoregulation, universal blood compatibility, and adaptation to high-altitude environments.
A Phased Approach to Innovation
DARPA has structured the Smart-RBC program as a 36-month effort, divided into two 18-month phases.
Phase I will require research teams to demonstrate proof-of-concept. The primary goal is to show that the synthetic biological circuits can be successfully integrated during the differentiation of stem cells into red blood cells and, crucially, that these circuits remain functional after the mature red blood cells eject their nuclei—a key stage in their development.
Phase II will focus on refining the system, demonstrating enhanced performance, and culminating in a practical capability demonstration to validate the technology.
The program is being led by Dr. Christopher Bettinger, a Technical Point of Contact and Program Manager in DARPA's Biological Technologies Office. To encourage broad participation, the agency is directing potential new partners to DARPAConnect, a resource designed to guide newcomers through the agency's contracting process.
While still in its nascent stages, the Smart-RBC initiative signifies the Pentagon's growing investment in synthetic biology as a critical defense capability. By seeking to program biology itself, DARPA aims to fundamentally improve the survivability, endurance, and adaptability of military personnel in the face of increasingly harsh and unpredictable operational environments.
