The Defense Advanced Research Projects Agency (DARPA) wants to move protein purification beyond the “one protein, one ligand” model. Its upcoming Protein Palace program aims to develop a universal, tunable platform capable of rapidly purifying virtually any protein with high specificity, purity, and yield. The goal is to overcome a costly, time-consuming bottleneck that limits the production and accessibility of high-value biomacromolecules.
DARPA’s Multi X Office will host an in-person Proposers Day on November 17, 2026, to introduce the program’s technical objectives and connect potential performers.
Key Dates and Details
| Detail | Information |
|---|---|
| Program / Special Notice | Protein Palace / DARPA-SN-27-01 |
| Proposers Day | November 17, 2026, from 9 a.m. to 4 p.m. ET |
| Location | Executive Conference Center, 4075 Wilson Blvd., Suite 300, Arlington, VA |
| Registration deadline | November 9, 2026, at 4 p.m. ET, or earlier if capacity is reached |
Why Protein Purification Needs a Different Approach
Producing a protein is only part of the biomanufacturing challenge. Separating it from host proteins and other impurities, while maintaining its biological activity, often requires extensive downstream process development. Conventional capture methods rely on a “lock-and-key” relationship between a target protein and a specific ligand, followed by additional purification steps. Developing those methods can be lengthy, with no guarantee of success.
That lack of flexibility creates a problem for applications that require timely access to diverse proteins. Previous DARPA programs have invested in protein synthesis and new defense applications for proteins. Protein Palace addresses the downstream challenge: obtaining those proteins at the purity needed to use them. Its intended impact extends beyond biological therapeutics to mission-critical biomacromolecules supporting current and emerging Department of War needs.
What Protein Palace Aims to Build
The program seeks to break the traditional tradeoff between generalizability and specificity. Rather than developing a custom purification method for each new target, performers will pursue a platform that can be tuned to separate different proteins with high purity and yield.
DARPA is interested in dynamic chemical and physical approaches that exploit the distinct physicochemical characteristics of individual proteins. These approaches should move beyond rigid, predefined binding pockets, affinity tags, and nonspecific separation methods to distinguish subtle differences between proteins.
The intended result is a reconfigurable system that can adapt across proteins with different structures and functions. If successful, it could reduce the time and cost of downstream processing while accelerating production, scale-up, and access to high-value biological materials.
From Small-Scale Feasibility to Scalable Purification
Protein Palace is planned as a 42-month program with two phases:
Phase 1: Specificity and generalizability, 24 months. Performers will demonstrate a purification platform and process capable of separating eight different proteins at small scale, with purity and yield comparable to the state of the art. The emphasis is on proving that the platform can be tuned to work across different protein types.
Phase 2: Scalability and throughput, 18 months. Performers will develop and deliver a scaled-up platform with increased purity, yield, volume, and throughput. They must also demonstrate purification of two additional difficult-to-purify proteins that cannot be separated using state-of-the-art methods.
Performers will propose a panel of proteins representing a broad range of structures and functions, along with their relevance to defense applications. DARPA will select the protein used for the initial demonstration so an independent verification and validation team can evaluate approaches using a common starting feedstock.
What This Means for Prospective Performers
The program’s ambition is not simply a better purification process for one target. It is a platform that maintains specificity while adapting to diverse proteins and scaling to relevant quantities. Prospective teams should evaluate their capabilities against that broader objective.
Key questions to consider include:
What makes the platform tunable across proteins with different structures and functions?
How will the approach achieve high purity and yield while preserving biological activity?
What evidence supports a path from small-scale separation to increased throughput?
Where could partners strengthen the team’s separation science, platform engineering, scale-up, or application expertise?
Proposers Day and Next Steps
The November 17 event will introduce the program’s vision and goals and provide opportunities for interaction and teaming among potential performers. Registration and required access forms are due November 9, 2026, at 4 p.m. ET, with registration closing earlier if capacity is reached.
Note: This announcement is a Proposers Day special notice, not a solicitation for proposals or abstracts. DARPA anticipates releasing the program solicitation before the event through SAM.gov. Attendance is not required to respond to a subsequent solicitation.
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For additional information on where your capabilities could plug into this upcoming program, schedule a conversation with our team.
