Protein ENGineering (PENG)
DARPA is soliciting innovative proposals for the PENG program, which aims to develop a multifunctional, target-agnostic platform for precise, programmable editing of endogenous proteins. The program seeks to transform proteome engineering from isolated, bespoke tools into a universal, software-defined discipline. The integrated platform will combine modular targeting, generalizable effector chemistries, and multiplexed control systems, leveraging novel splicing, ligation, and co-translational techniques. Performers are expected to explore multiple technical paths, advancing from foundational validation to robust demonstrations of efficacy. Final validation will occur in high-fidelity cellular models such as organoids to provide tissue-level proof-of-concept.