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The US Defense Advanced Research Projects Agency’s (DARPA) RBC-Factory program aims to add peptides, proteins or pigments to red blood cells to confer broad, durable, reversible protection for warfighters.
American and allied warfighters operate in environments that place significant stress on the body and present conditions that can compromise health and reduce operational readiness. Stressors may include too much or too little oxygen, extreme heat or cold, pathogens or endemic diseases such as malaria.
Accordingly, these warfighters often face these challenges with limited or no physiological preparation or protection. Greater preparedness prior to deployment and sustained protection while on operations is essential to enable personnel to perform effectively in such demanding environments.
Dr Christopher Bettinger, RBC-Factory program manager, explained the importance of this new research program, saying, “The current state of the art to maintain and protect warfighters operating in extreme environments or facing potential threats requires administration of pre-exposure prophylaxes or post-exposure medical countermeasures.”
To address these challenges, DARPA’s RBC-Factory program aims to develop a platform to modify human red blood cells (RBC) by incorporating additional biologically active components. These modifications are intended to provide warfighters with enhanced protection and enable them to function more effectively in extreme or high-threat environments.
Specifically, modified RBCs (mRBC) will be engineered to include peptides, proteins or pigments that offer broad yet reversible protection to the recipient over extended durations.
In order to respond to these challenges and avoid long-term impacts to individual soldiers, Dr Bettinger added, “these approaches produce side effects, have limited efficacy and can be costly. They also present logistical challenges like carrying bulky personal protective equipment or cognitive burdens such as taking oral medications with specific regimes and schedules. RBC-Factory aims to create a device-based approach to imbue RBCs with novel cargoes while precluding genetic modification”.
If successful, the 21-month program will deliver two key outcomes:
- A durable knowledge base: Performers will define the physical and chemical limits of what can be inserted into an RBC. The program will also evaluate the effects – or lack thereof – of introducing novel bioactive molecules and materials on RBC physiological properties. This knowledge base will establish the experimental and practical boundaries for what materials can be incorporated into RBCs.
- A medical device prototype: The program will deliver a prototype device capable of modifying RBCs at high rates to meet anticipated operational needs. Performer progress across all activities will be verified by independent verification and validation (IV&V) partners.
The RBC-Factory program will also address ethical, legal and societal implications (ELSI) associated with the development and use of mRBC platforms. Regular consultations between performers, IV&V teams, and ELSI specialists will ensure discussions around acceptance, adherence and equity impacts are incorporated into the development process. These consultations will document key concerns and inform the responsible advancement of the technology.
