Which program will fund this topic?
What type of proposals will be accepted?
Both Phase I and Direct to Phase II (DP2)
Technology Area(s): Biomedical
The Defense Advanced Research Projects Agency (DARPA) Small Business Programs Office
(SBPO) is issuing an SBIR/STTR Opportunity (SBO) inviting submissions of innovative
research concepts in the technical domain(s) of Biomedical. In particular, DARPA is interested
in understanding the feasibility of rapid, flexible manufacturing of DNA molecules for synthetic
biology and therapeutic applications.
This SBO is issued under the Broad Agency Announcement (BAA) for SBIR/STTR,
HR001120S0019. All proposals in response to the technical area(s) described herein will be
submitted in accordance with the instructions provided under HR001120S0019, found here:
The eligibility requirements for the SBIR/STTR programs are unique and do not
correspond to those of other small business programs. Please refer to Section 3.1, Eligible
Applicants, of HR001120S0019 for full eligibility requirements.
b. Anticipated Structure/Award Information
Please refer to Section 1, Funding Opportunity Description, in HR001120S0019 for
detailed information regarding SBIR/STTR phase structure and flexibility.
If a proposer can provide adequate documentation to substantiate that the scientific and
technical merit and feasibility described in the Phase I section of the topic has been met
and describes the potential commercial applications, the Direct to Phase II (DP2)
authority allows the Department of Defense (DoD) to make an award to a small business
concern under Phase II of the SBIR program without regard to whether the small business
concern was provided an award under Phase I of an SBIR program. This SBO is
accepting both Phase I and DP2 proposal submissions.
For this SBO, DARPA will accept Phase I proposals for cost of up to $225,000 for a 12-
month period of performance.
DARPA will accept DP2 proposals for cost of up to $1,750,000. This includes a 24-
month base period not to exceed a cost of $1,000,000 and a 12-month option period not
to exceed a cost of $500,000. A separately priced option of up to $250,000 may also be
proposed for contractors who would like to be considered for participation in the DARPA
Embedded Entrepreneur Initiative (EEI). Refer to Section 2.6 of HR001120S0019 for
detailed information on EEI.
Proposers should refer to Section 4, Application and Submission Information, of
HR001120S0019 for detailed proposal preparation instructions. Proposals that do not
comply with the requirements detailed in HR001120S0019 and the research objectives of
this SBO are considered non-conforming and therefore are not evaluated nor considered
Phase I proposals shall not exceed 20 pages. Phase I commercialization strategy shall not
exceed 5 pages. This should be the last section of the Technical Volume and will not
count against the 20-page limit. Please refer to Appendix A of HR001120S0019 for
detailed instructions on Phase I proposal preparation.
DP2 Feasibility Documentation shall not exceed 40 pages. DP2 Technical Proposal shall
not exceed 40 pages. Phase II commercialization strategy shall not exceed 5 pages. It
should be the last section of the Technical Volume and will not count against the 40-page
limit. Please refer to Appendix B of HR001120S0019 for detailed instructions on DP2
c. Evaluation of Proposals
Section 5, Evaluation of Proposals, in HR001120S0019 provides detailed information on
proposal evaluation and the selection process for this SBO.
d. Due Date/Time
Full proposal packages (Proposal Cover Sheet, Technical Volume, Price/Cost Volume
inclusive of supporting documentation, and Company Commercialization Report) must
be submitted via the DoD SBIR/STTR Proposal Submission website per the instructions
outlined in HR001120S0019 no later than 2:00 pm ET,
April 20, 2020.
Develop a rapid and cost-effective synthetic DNA manufacturing capability.
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:
c. Phase I
Develop rapid DNA synthesis method(s) 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 I deliverables: Basic prototype of the DNA synthesis platform and a final report
that must include: (1) proposed methods to scale DNA synthesis towards production
levels capable of generating more than 500 unique sequences; (2) prototype performance
metrics; (3) results of the capability demonstration; and (4) competitive assessment of the
Plans for Phase II should include optimization design goals and key technological
milestones to scale no less than 500 and up to 1000 or more unique DNA molecules in
Proposers interested in submitting a Direct to Phase II (DP2) proposal must provide
documentation to substantiate that the scientific and technical merit and feasibility
described above has been met and describes the potential commercial applications.
Documentation should include all relevant information including, but not limited to:
technical reports, test data, prototype designs/models, and performance goals/results. For
detailed information on DP2 requirements and eligibility, please refer to Section 4.2,
Direct to Phase II (DP2) Requirements, and Appendix B of HR001120S0019.
d. Phase II
Develop and 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.
i. Schedule/Milestones/Deliverables – Phase II fixed payable milestones for this program should include:
Phase II deliverables: Working prototype of the multiplexed system and a final report that
includes: (1) system performance metrics; (2) results of the capability demonstration; and
(3) projections for commercial scale manufacturing yield and costs.
e. Dual Use Applications (Phase III)
The commercial applications of synthetic DNA include, but are not limited to,
applications for synthetic biology, manufacturing of protein therapeutics, and drug
discovery modalities. These technologies create potential for the use of DNA
technologies in cancer immunotherapy. DoD/military applications include generation of
synthetic biology components required to produce DoD relevant materials and for the
manufacturing of DNA-encoded antibodies and vaccines to provide protection against
(1) Randall A. Hughes and Andrew D. Ellington. Synthetic DNA Synthesis and
Assembly: Putting the Synthetic in Synthetic Biology. Cold Spring Harb Perspect Biol.
2017 Jan 3;9(1).
(2) Palluk S. et. al. De novo DNA synthesis using polymerase-nucleotide conjugates. Nat
Biotechnol. 2018 Aug;36(7):645-650. doi: 10.1038/nbt.4173. Epub 2018 Jun 18.
DNA, manufacturing, synthesis, formulation, delivery, synthetic biology
DARPA intends to use electronic mail for all correspondence regarding this SBO. Questions
related to the technical aspect of the research objectives and awards specifically related to this
SBO should be emailed to HR001120S0019@darpa.mil. Please reference BAA
HR001120S0019-02 in the subject line. All questions must be in English and must include the
name, email address, and the telephone number of a point of contact.
DARPA will attempt to answer questions in a timely manner; however, questions submitted
within seven (7) calendar days of the proposal due date listed herein may not be answered.
DARPA will post a consolidated Frequently Asked Questions (FAQ) document. To access the
posting please visit: http://www.darpa.mil/work-with-us/opportunities. Under the
HR001120S0019-02 summary, there will be a link to the FAQ. The FAQ will be updated on an
ongoing basis until one week prior to the proposal due date.
In addition to the FAQ specific to this SBO, proposers should also review the SBIR/STTR
General FAQ list at: http://www.darpa.mil/work-with-us/opportunities?tFilter=&oFilter=29934.
Under the HR001120S0019 summary, there is a link to the general FAQ.
Technical support for the Defense SBIR/STTR Innovation Portal (DSIP) is available Monday
through Friday, 9:00 a.m. – 5:00 p.m. ET. Requests for technical support must be emailed to
DoDSBIRSupport@reisystems.com with a copy to HR001120S0019@darpa.mil.
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