Folded Non Natural Polymers with Biological Function (Fold F(x)) | Apply Online

FAQs: DARPA Fold F(x) (DARPA-BAA-14-13)

What is the DARPA Fold F(x) opportunity?

Fold F(x) (Folded Non-Natural Polymers with Biological Function) was a DARPA Defense Sciences Office research and development opportunity under Funding Opportunity Number DARPA-BAA-14-13. It sought end-to-end capabilities to create and use entirely new classes of biological-like molecules that go beyond natural biology.

What was DARPA trying to build through Fold F(x)?

DARPA wanted a repeatable "discovery engine" that can rapidly generate, test, read out (decode), and scale up folded, non-natural, sequence-defined polymers that perform useful biological functions. The intent was to achieve capabilities analogous to proteins and nucleic acids, but using chemistries not limited to natural amino acids or nucleotides.

What does "Folded Non-Natural Polymers with Biological Function" mean in this program?

In the Fold F(x) context, it refers to polymers that are (1) non-natural (built from non-natural backbones and/or building blocks), (2) sequence-defined (the order of monomers is controlled), (3) capable of folding into functional shapes, and (4) able to carry out biological-like functions such as target binding or catalysis.

What kinds of molecules were of interest?

The program emphasized folded, non-natural, sequence-defined polymers designed to function like next-generation antibodies (binding agents) and enzymes (catalysts), while enabling new structures and functions that standard biological polymers cannot provide.

What are "sequence-defined polymers" and why did DARPA emphasize them?

Sequence-defined polymers are polymers whose monomer order is intentionally controlled and can be determined later. DARPA emphasized this because the ability to identify and reproduce "winning" sequences (after screening/selection) depends on knowing what those sequences are, similar to how protein or nucleic-acid sequences are read out in biological discovery workflows.

What does "end-to-end process" mean for this opportunity?

It refers to a complete workflow that includes rapid library generation, screening or selection against a target, enrichment of high performers, identification/decoding of hit structures (sequence readout), and evidence that successful polymers can be scaled up for larger production and broader use.

What were the primary technical focus areas?

Fold F(x) placed major emphasis on two outcomes: (1) non-natural affinity reagents (binding agents) and (2) non-natural polymer-based catalytic systems (catalysts that synthesize or degrade target molecules).

What is an "affinity reagent" in the context of Fold F(x)?

An affinity reagent is a molecule that binds a chosen target with high specificity and strong binding strength, similar in concept to antibodies or aptamers, but built from non-natural polymer backbones or building blocks.

Did DARPA want affinity reagents that only bind targets, or also do more?

The description indicates DARPA was interested in binding agents that could potentially do more than bind, including responding in useful ways upon binding (for example, signal generation or conditional behavior).

What does the program mean by "catalytic systems"?

Catalytic systems in Fold F(x) refer to non-natural polymer-based catalysts that could either synthesize a desired target molecule or degrade a target. The emphasis was on fast, selective chemical transformations relevant to mission needs.

What applications did DARPA associate with the catalytic component?

The opportunity text points to applications including sensing, countermeasure development, decontamination, and other mission-relevant biochemical and chemical tasks where selective and rapid chemistry is valuable.

How large were the polymer libraries expected to be?

DARPA expected strong performers to invent or integrate synthetic approaches capable of producing extremely large libraries of non-natural, sequence-defined polymers on the order of 10^9 distinct members.

Why was a library size of about 10^9 important?

The solicitation framed this scale as comparable to powerful biological selection methods (such as phage display or nucleic-acid aptamer selection). The challenge was achieving similar scale while using non-natural chemistries and maintaining sequence definition and decodability.

What screening or selection capabilities were expected?

DARPA sought flexible screening and selection strategies capable of reliably extracting rare, high-performing binders (high affinity and specificity) and catalysts (high activity and selectivity) from vast libraries. The platform was expected to be adaptable so it could be redirected to new targets without a complete redesign.

What performance characteristics mattered for binders?

For affinity reagents, the solicitation emphasized high affinity (strong binding) and high specificity (selective binding to the intended target).

What performance characteristics mattered for catalysts?

For catalysts, the solicitation emphasized high activity (effective catalysis) and high selectivity (favoring the desired reaction or transformation over undesired ones).

What was the "four-day" metric mentioned in the opportunity?

Fold F(x) emphasized speed by expecting a successful approach to be able to produce, through screening/selection, a functional affinity reagent or catalyst against a Department of Defense interest target in roughly four days.

What does the four-day goal imply about the workflow?

It implies the workflow needed to be streamlined across steps that commonly slow molecular discovery, including library generation, target exposure, enrichment, hit identification, and sequencing/decoding of winning polymer structures.

What does DARPA mean by scalability and transferability?

The program required evidence that the capability could scale to larger production and be transferred beyond a single bespoke laboratory setup. It also suggested an emphasis on standardized protocols, reproducible methods, and pathways to manufacturing or distribution so the broader DoD science and technology community could use it.

Was the solicitation open to different types of applicants?

Yes. Eligibility was described as unrestricted, indicating the solicitation was open to a wide range of applicants (such as universities, companies, nonprofits, and other organizations), subject to any additional clarifications in the full announcement.

What types of award instruments could DARPA use for this opportunity?

The opportunity allowed multiple award instruments, including cooperative agreements, grants, other transactions, and procurement contracts, reflecting DARPA's flexibility in structuring collaborations based on the work and anticipated government involvement.

What was the activity category for this opportunity?

It was listed under Science and Technology and other Research and Development.

What CFDA number was referenced?

The announcement referenced CFDA 12.910 (Research and Technology Development).

When was the opportunity posted and when did it close?

The solicitation was posted on January 7, 2014. The original and current closing date listed was April 3, 2014.

Was this opportunity still active at the time described?

No. The listing notes it was archived on June 3, 2014.

Where were the full details located?

The full details were provided in the attached DARPA BAA 14-13 documentation.

What if someone had trouble accessing the announcement electronically?

The notice stated that applicants needing help accessing the announcement electronically could contact the BAA Coordinator.

What is the bottom-line goal of Fold F(x) in plain terms?

The program aimed to enable rapid, scalable discovery of non-natural polymers that fold into functional shapes and can act like advanced binders and catalysts, with a repeatable pipeline that can be quickly aimed at new defense-relevant targets and used across the DoD research ecosystem.