Rapid Inhibitor Discovery and Development pipeLine (RIDDL)

• The Defense Advanced Research Projects Agency (DARPA) is soliciting 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.

The Rapid Inhibitor Discovery and Development pipeLine (RIDDL) program explicitly seeks transformative approaches that enable the rapid discovery, design, and development of novel inhibitors of gene editing technologies with enhanced activity, specificity, utility, and potency. These approaches could serve as a rapid response to 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. Research that generates incremental improvements to the existing state-of-the-art is specifically excluded.