The Defense Advanced Research Projects Agency (DARPA), through its Biological Technologies Office (BTO), has announced a groundbreaking solicitation titled DARPA-PS-26-02: Smart Red Blood Cells (Smart-RBC) to redefine human performance in extreme environments. This program seeks to leverage advances in synthetic biology and bioengineering to create red blood cells (RBCs) that can temporarily and safely modify human physiology. DARPA’s vision is to establish a new class of “smart” blood products capable of sensing biological cues, making autonomous decisions, and responding with tailored physiological effects to enhance survivability and endurance in operational settings.
Overview of the Smart-RBC Program
The Smart-RBC initiative aims to engineer red blood cells that go beyond oxygen transport, creating cells that can act as biological platforms to detect, decide, and deliver targeted responses. Through embedded biological circuits, these “Smart Red Blood Cells” (SRBCs) will include three integrated layers of function:
- Sense: detect extracellular biomarkers related to metabolism or trauma.
- Decide: interpret those signals through logic gates and biological computation.
- Act: trigger effector molecules that influence physiology, metabolism, or hemostasis.
DARPA has identified two primary use cases for the program:
- Increasing exercise tolerance, by optimizing metabolic pathways to sustain performance in high-exertion or high-altitude conditions.
- Accelerating hemostasis, by detecting trauma and activating blood clotting pathways to prevent critical blood loss.
Performers will develop these SRBCs by engineering red blood cell precursors rather than modifying mature cells to maintain safety and scalability. The program emphasizes that all SRBCs must be enucleated (without a nucleus) to prevent the transfer of genetic material, ensuring biosafety for future human applications.
Program Structure and Technical Goals
DARPA’s Smart-RBC program is a 36-month effort divided into two main phases, with a final capability demonstration:
- Phase I (18 months): Address Technical Challenge 1 (TC#1) to produce, position, and retain novel proteins in mature RBCs while meeting DARPA-defined safety and efficiency metrics.
- Phase II (18 months): Address Technical Challenge 2 (TC#2) to develop fully functional SRBCs with integrated sense–decide–act circuits capable of modulating physiology.
- Capability Demonstration (CD): Validate SRBC performance using in vitro or in vivo models to show functional, measurable physiological outcomes.
DARPA will coordinate the program through dedicated support teams, including Testing and Evaluation (T&E), Eligibility, Adoption, and Adherence (EAA) assessments, and Regulatory Engagements with the FDA’s Center for Biologics Evaluation and Research (CBER). These components ensure scientific rigor, ethical oversight, and early alignment with regulatory pathways.
Key Dates for Proposers
Interested proposers should mark the following milestones:
- Abstract Questions Due: November 3, 2025, 12:00 PM ET – final date to submit clarification questions.
- Abstracts Due: November 12, 2025, 12:00 PM ET – required for eligibility to advance.
- Oral Proposal Package (OPP) Due: January 14, 2026, 12:00 PM ET – invited proposers submit their full package.
- Oral Presentations: January 21–22, 2026 – in-person presentations at DARPA headquarters in Arlington, VA.
Funding and Award Structure
DARPA anticipates multiple awards under this solicitation, supported by a total of approximately $35.1 million in available funding.
Awards will be issued as Other Transactions (OTs) for Prototype, which allow for flexible, innovation-driven agreements between DARPA and performers. Each award is expected to support up to 36 months of performance, covering both research and demonstration phases. Proposers are encouraged to form multidisciplinary teams that integrate expertise in synthetic biology, hematology, systems biology, and bioengineering.
Transforming Human Health and Performance
DARPA’s Smart-RBC program is more than a defense initiative; it is a bold step toward programmable biology. By enabling red blood cells to act as intelligent biological agents, this research could one day support battlefield resilience, emergency medicine, and civilian healthcare. Applications may extend from enhanced metabolic recovery for first responders to precision control of clotting during surgery.
The Smart-RBC program embodies DARPA’s long-standing mission to expand the boundaries of what is biologically possible while ensuring safety, scalability, and ethical use.
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