DARPA’s Biological Technologies Office is seeking innovative proposals to develop and demonstrate rapid methods to identify and optimize novel molecules that exhibit inhibitory effects on gene editing technologies. Of particular interest are commonly used gene editors such as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated proteins (CRISPR-Cas) nucleases; gene editing technologies beyond CRISPR-Cas systems are also of interest to keep pace with the rapidly advancing field and promote the safe, controlled use of these technologies.
RIDDL explicitly seeks transformative approaches that enable the rapid discovery, design, and development of novel inhibitors with enhanced activity, specificity, utility, and potency for gene editing technologies. These approaches could serve as a rapid response to counteract the accidental or intentional misuse of gene editing technologies. Novel inhibitor activity will be assessed in vitro over the course of the program to demonstrate the efficacy of the prototype discovery and development pipelines. The pipelines, as well as a subset of top-performing molecules at scaled-up quantities, will be transitioned for testing and evaluation by Department of Defense (DoD) stakeholders.
The program has three phases of 10 months each:
- Phase 1 – Base – establish discovery and test platforms.
- Phase 2 – Option – improve pipeline by identifying potential inhibitors for novel gene editors and developing in vitro test systems to test those inhibitors.
- Phase 3 – Option – demonstrate ability of platforms to rapidly produce highly potent inhibitors; validate discovery pipeline candidates and in vitro models to demonstrate inhibition of novel gene editors.
DARPA is specifically NOT interested in proposals that involve:
- Engineering Cas variants with modulated activity and their cognate inhibitors with enhanced specificity
- Approaches that include animal or human subjects research
- Solely in silico approaches without corresponding wet lab validation
- Approaches that do not develop inhibitors for Cas9 enzymes and Cas12 enzymes
Full proposals are due 20 December 2024.
Document
Program Solicitation – RIDDL: DARPA-PS-25-03
