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DARPA Seeks Innovations in Rapid DNA Molecule Manufacturing

Biodefense Industry News

DARPA is interested in understanding the feasibility of rapid, flexible manufacturing of DNA molecules for synthetic biology and therapeutic applications.

Small business interests are invited to submit innovated concepts under a new funding opportunity from the Defense Advanced Research Projects Agency (DARPA).

There is a critical DoD need to be able to rapidly and efficiently synthesize highly accurate kilobase (kb) pair length DNA constructs for medical countermeasure and synthetic biology applications.

Several DARPA programs and technologies (e.g., Living Foundries, PRemptive Expression of Protective Alleles and Response Elements (PREPARE), and Pandemic Prevention Platform (P3) rely heavily on synthetic DNA and the timely generation, manipulation, and delivery of genetic constructs. Current synthetic DNA production is costly, time-consuming, and requires highly specialized technical expertise and equipment. Consequently, few commercial suppliers are capable of producing synthetic DNA at a length that is appropriate for DARPA technologies (i.e., >2,500 base pairs) in the days-long turnaround time required for rapid response.

First, due to the limited capability base, commercial sources experience significant backlog in synthetic DNA production services, extending research and development timelines dependent on gene-encoded products, and increasing costs for the consumer. Second, current methods for synthesis or assembly of kilobase length constructs are often error prone, requiring manual purification and/or analytics steps to achieve the final product. Third, as demand for synthetic DNA production increases, any achieved throughput increases will need to maintain or even decrease the cost per base pair.

To achieve these goals, DARPA seeks methods capable of rapidly generating a panel of

synthetic DNA meeting the following objectives:

  • Each product sequence must be greater than 2,500 base pairs
  • Demonstrate a platform error rate of less than 1 per 5000 base pairs
  • Synthesis of at least 200 unique sequences (Phase I) in under one week
  • Synthesis of at least 500 unique sequences (Phase II) in under one week
  • Technology and commercial model with a cost per base pair to the consumer comparable to current vendors

For this opportunity, DARPA will accept Phase I proposals for costs of up to $225,000 for a 12-month period of performance. If a proposer can provide adequate documentation to substantiate that the scientific and technical requirements have been met, Direct to Phase II (DP2) authority may be exercised for proposals up to for costs of up to $1,750,000 (for a 24-month base period).

The objective of Phase I is to develop rapid DNA synthesis methods capable of generating DNA molecules greater than 2,500 base pairs in length. The synthesis method should be capable of producing 200 unique DNA sequences in less than one week in quantities sufficient for downstream cloning into expression vectors. Within the one-week production timeframe, the synthesized DNA molecules will need to be purified and analyzed for sequence identity relative to the input sequence and any residual impurities. At the end of Phase I, performers will need to demonstrate feasibility for producing 200 unique DNA sequences based on DARPA-defined targets in less than one week.

Phase II aims to demonstrate a flexible, multiplexed platform for the rapid synthesis of DNA molecules based on the basic prototype developed during Phase I. The platform should enable scaled synthesis of at least 500 unique gene sequences but preferably 1,000 unique sequences. Additionally, the platform at scale should generate products at a cost of <$0.01 per base pair. At the end of Phase II, performers will demonstrate the feasibility of producing 500-1000 unique DNA sequences based on DARPA-defined targets in less than one week.

Additional details are available at the federal contracting website under Notice ID: HR001120S0019-02. The response deadline is Apr 20, 2020 05:00 pm EDT.

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