Protein ENGineering (PENG)

The Defense Advanced Research Projects Agency (DARPA) seeks innovative proposals for development of a multifunctional, target-agnostic platform for precise, programmable editing of endogenous proteins, with an abstract due August 24, 2026, at 4:00 p.m. ET and tentative full proposals due October 19, 2026, at 4:00 p.m. ET. Multiple awards are anticipated using Other Transaction Agreements for Prototype vehicles. This is unrestricted competition.

The 42-month program spans three phases: Phase 1A (18 months), Phase 1B (6 months option), and Phase 2 (18 months option). Performers must develop integrated platforms combining three core capabilities: programmable targeting using generative AI models, generalizable chemistry (including logic-gated inteins or co-translational editing), and multiplexing capability for simultaneous, non-interfering edits. Work is performed at proposer facilities and must include laboratory infrastructure spanning computational structural biology, protein biochemistry, synthetic biology, and cell/tissue biology. NAICS code is 541714, Research and Development in Biotechnology.

Editing efficiency targets are 50% of nascent proteins edited over 8 weeks in Phase 1 and 75% across diverse proteins over 4 weeks in Phase 2. Performers must demonstrate at least three distinct protein family edits (globular, transmembrane, and fibrous proteins) and stable edited protein longevity of hours to days in Phase 1; greater than 3 weeks in Phase 2. Phase 1B serves as a capability demonstration gate requiring editing of DARPA-chosen protein targets. Phase 2 translates platforms into higher-order biological systems and includes a go-to-market strategic plan.

The solicitation explicitly excludes permanent genomic editing (CRISPR-Cas9, viral gene therapies), pure in silico modeling without wet-lab validation, traditional pharmacology, human subjects research, and post-translational tagging strategies like PROTACs. Fundamental research is expected to remain free from publication restrictions; proposers must indicate whether their research qualifies as fundamental. Non-U.S. organizations cannot participate. Performers must achieve CMMC Level 1 cybersecurity compliance by end of Phase 1A and become CUI-compliant before Phase 1B participation. Cost sharing applies only to traditional defense contractors not working with nontraditional contractors. Optional student programs include the DSO Fundamental Defense Research Talent Award (up to $150,000 per year for universities) and the DSO Industry Immersion Program (up to $160,000 per student for industry with university subcontractors). Contact: PENG@darpa.mil.