DARPA’s Defense Sciences Office seeks innovative proposals for the development of a multi-functional, target-agnostic platform for precise, programmable editing of endogenous proteins.
The PENG program seeks to transform proteome engineering from a collection of isolated, bespoke tools into a universal, software-defined discipline.
PENG 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 (eg organoids), to provide an integrated proof-of-concept at the tissue level.
Performers will be expected to deliver a fully integrated editing prototype platform capable of executing multiplexed, on-demand modifications to endogenous proteins.
The culminating prototype deliverable will be a validated system that provides tunable, reversible, and context-dependent control over physiological functions, achieving transient, mechanism-based therapeutic outcomes without requiring permanent genomic modifications or relying on pharmacological approaches. The prototype platform should demonstrate robust adaptability and rapid programmability against diverse, previously unannounced protein targets and achieve multiple point-specific, measurable and functional outcomes in complex tissue models and animal models.
PENG is a 42-month, multi-phase effort:
Phase 1A (Base): Platform Foundations – 18 months – establishment of foundational biochemistry; validation of platforms using self-selected protein targets; successfully edit targets spanning at least 3 distinct structural protein families (eg globular, transmembrane, fibrous proteins).
Phase 1B (Option Period 1) – Capability Demonstration – 6 months – edit previously unannounced target proteins under short-notice constraints within complex tissue systems.
Phase 2 (Option Period 2) – Advanced System Integration– 18 months – translating validated editing platforms into higher-order biological systems; transition from tissue models to complex cellular systems; optimising kinetics, safety and delivery parameters.
Abstract proposals are due 24 August 2026.
Document
Program Solicitation – PENG – HR001126S0016-Amendment-01
