DARPA Opens Protein Palace Solicitation for Tunable Protein Purification Platforms

Key Dates and Submission Details

Abstracts and proposals must be submitted through BAAT. The required intent to propose must be emailed to [email protected]. Full proposals include written materials and an oral presentation, with instructions and templates provided in the solicitation attachments.

What Is DARPA Seeking Through Protein Palace?

Protein purification remains a difficult downstream manufacturing problem because a target protein must be separated from a mixture containing host-cell proteins, cellular debris, nucleic acids, lipids, salts, and other components. Conventional methods combine broadly applicable separations based on properties such as charge and size with highly specific affinity approaches that require customized development.

Protein Palace seeks a reconfigurable system that can distinguish subtle physicochemical differences between proteins and adapt across targets while preserving biological function. DARPA is interested in dynamic chemical and physical approaches that achieve specificity without relying on fixed binding pockets or affinity tags. Research primarily producing incremental improvements to existing practice is explicitly excluded.

The platform must output properly folded, functional proteins. Proposed approaches must address at least eight protein categories, with examples including enzymes, structural proteins, signaling or receptor proteins, transport proteins, nucleic acid binding proteins, and motor proteins. At least one target must function as a multimeric protein containing multiple subunits.

Technical Targets: From Eight Protein Categories to One-Week Method Development

Protein Palace is structured in two phases, with an anticipated downselect at month 12 following demonstration of purification of three proteins. Progression to Phase 2 depends on funding availability and performance against Phase 1 metrics.

Each protein is purified as a separate task. Performers must demonstrate the functionality of the resulting protein; the metrics do not call for simultaneous purification of all targets from one feedstock.

During Phase 1, an independent verification and validation team will evaluate approaches using a DARPA-defined protein and common starting feedstock. Phase 2 adds a performer-proposed challenge protein from a category that cannot be purified using current state-of-the-art methods, plus a DARPA-provided target used to test one-week method development.

Which Approaches Are Outside the Program’s Scope?

The solicitation excludes several approaches that could otherwise simplify a laboratory demonstration:

• Separating proteins artificially added, or “doped,” into a feedstock.

• Adding affinity tags.

• Developing a method applicable to only one protein category.

• Extensively processing feedstocks before they enter the platform.

• Denaturing proteins.

• Requiring subsequent processing to restore proper folding and functionality, although buffer adjustments are permitted.

These constraints make feedstock selection and functional testing important early proposal decisions. Teams must identify their target proteins, explain how feedstocks will be acquired or generated, and describe assays that establish protein functionality. Proposed methods must also be able to purify host or endogenous proteins.

Commercial Viability and Execution Requirements Matter

DARPA requires a technoeconomic analysis examining technical feasibility and economic viability. Approaches should reduce costs relative to current methods and support proteins with lower market values than pharmaceutical products. Transition planning must address both research-scale applications for government partners and larger commercial-scale use.

The award structure also has practical implications for pursuit planning:

• Milestone payments: Payments will follow government technical verification and written acceptance of defined deliverables. Teams must align proposed payment amounts with technical progress, working-capital needs, and verifiable outputs.

• Resource sharing: DARPA encourages cash or in-kind resource contributions where practicable. The solicitation does not prescribe a single fixed sharing percentage.

• Intellectual property: Performers retain ownership of background and foreground intellectual property. The government expects at least Government Purpose Rights in foreground intellectual property, with additional provisions governing verification access, commercialization, and potential changes in rights.

• Cybersecurity and publication: Cybersecurity Maturity Model Certification (CMMC) Level 1 self-assessment is required at award, with Level 2 self-assessment required before month 12 or milestone 5, whichever occurs first. DARPA anticipates non-fundamental research restrictions and requires public-release review before dissemination.

Teams considering National Lab, federally funded research and development center, or university affiliated research center partners should review the solicitation’s specific participation rules before committing to a team structure. Entities serving as government verification, testing, or advisory partners for Protein Palace are prohibited from joining performer proposals.

Preparing a Protein Palace Pursuit

DARPA will evaluate proposals in descending order of importance based on scientific and technical merit; potential contribution and relevance to its mission; and budget, price, and schedule. A competitive approach needs a credible connection between the separation mechanism, the diversity of the proposed protein panel, functional validation, and the ability to scale.

The abstract stage provides an early opportunity to present that approach before completing the full submission. Teams should also resolve feedstock access, partner roles, milestone economics, and security requirements early enough to inform the technical plan and price proposal.