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DARPA – Broad-Spectrum Antagonists for Editors (B-SAFE) – HR001124S0032

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DARPA – Broad-Spectrum Antagonists for Editors (B-SAFE) – HR001124S0032


DARPA’s Biological Technologies Office is seeking innovative proposals to identify and optimize novel molecules that exhibit inhibitory effects on Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated proteins (CRISPR-Cas) gene editing processes. The B-SAFE program explicitly seeks transformative approaches that enable the discovery or design of novel inhibitors of gene editing technologies with enhanced activity, utility, and breadth of coverage. The B-SAFE program is agnostic to the methods and approaches employed for discovery or design of novel inhibitors as long as they are potentially transformative.

Novel inhibitor activity will be assessed in vitro over the course of the program, and a subset of top performing molecules will be selected for scale-up at quantities sufficient for testing and evaluation. In concert, DARPA is interested in exploring methods to rapidly discover inhibitor molecules for novel gene editing technologies beyond CRISPR-Cas systems to keep pace with the rapidly advancing field and promote the safe, controlled use of these technologies.

B-SAFE has two Technical Areas which will run concurrently.  Proposals may address TA 1 only or both Technical Areas 1 and 2.  Proposals only addressing TA 2 will not be assessed.

TA 1- Inhibitors for DNA Editors – discovery, development, optimization and validation of broad-spectrum inhibitors for CRISPR-Cas DNA gene editors (ie Cas9 and Cas12 species)

TA 2 – Discovery Platform for Inhibitors of Novel Editors – design and implementation of a discovery platform for inhibitors of novel gene editing systems (eg Fanzor, OMEGA) and RNA editing systems (eg Cas13).

B-SAFE will have 3 sequential phases, each of 10 months duration, with progression from Phase I to Phase II and from Phase II to Phase III dependent on demonstrated success in meeting program metrics and objectives:

  • Phase I – Base – 10 months – establish discovery & test platforms;
  • Phase II  – Priced Option 1  – 10 months – TA 1 – optimize lead candidate inhibitors for potency and breadth; TA 2 – demonstrate pipeline developed in phase 1
  • Phase III – Priced Option 2 – 10 months – demonstrate ability of platforms to produce potent, broad-spectrum inhibitors.

Proposal abstracts are required and due 15 July 2024, with full proposals due 12 August 2024.


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Broad Agency Announcement – B-SAFE: HR001124S0032




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