Protein ENGineering (PENG) DARPA-PS-26-129

The Defense Advanced Research Projects Agency (DARPA) is soliciting innovative proposals for the development of a multifunctional, target-agnostic platform for precise, programmable editing of endogenous proteins. The goal of the Protein ENGineering (PENG) program is to transition proteome engineering from a collection of isolated, bespoke tools into a universal, software-defined discipline. The PENG program will establish a comprehensive, integrated platform composed of modular targeting, generalizable effector chemistries, and multiplexed control systems. Rather than developing isolated, target-specific tools, performers will integrate novel splicing, ligation, and co-translational techniques to directly recognize, modify, and rewrite endogenous proteins within complex biological architectures. Performers may explore multiple technical paths, progressively advancing their approaches from foundational validation to robust demonstrations of efficacy. Ultimately, this integrated platform will be validated in high-fidelity cellular models (e.g., organoids), to provide an integrated proof-of-concept at the tissue level.