DARPA is seeking innovative proposals to develop a multifunctional, target-agnostic platform for precise, programmable editing of endogenous proteins. The goal is to transform proteome engineering into a universal, software-defined discipline through an integrated platform combining modular targeting, generalizable effector chemistries, and multiplexed control systems. Performers will integrate novel splicing, ligation, and co-translational techniques to directly recognize, modify, and rewrite proteins within complex biological systems. Multiple technical paths may be explored, progressing from foundational validation to robust demonstrations of efficacy. The platform will ultimately be validated in high-fidelity cellular models, such as organoids, to provide tissue-level proof-of-concept.

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.