Research Opportunity: DNA-Protein Epigenetic Chemistry Engineering (D-PECHE)

DARPA-SN-26-67, Amendment 1, clarifies submission details for the DNA-Protein Epigenetic Chemistry Engineering (D-PECHE) Special Notice, a research opportunity under the broader HR001126S0003 announcement. The program seeks innovative proposals for developing novel mechanisms to write and erase epigenetic base modifications in DNA within a four-month period. Research should focus on in vitro validation in living cells, excluding established DNA methylases/demethylases, human/animal subjects research, and certain other areas. Proposals must address writing mechanisms, erasing mechanisms, or both, detailing their approach, feasibility, and validation methods. Abstracts are due May 27th, 2026, by 4:00 PM ET, with costs not exceeding $2,000,000 for accelerated awards. Submissions will be evaluated on scientific merit, relevance to DARPA's mission, and cost realism.

DARPA's Special Notice DARPA-SN-26-67 announces the DNA-Protein Epigenetic Chemistry Engineering (D-PECHE) research opportunity, soliciting proposals for novel mechanisms to write and erase epigenetic base modifications in DNA. This 4-month program seeks to de-risk the development of new epigenetic editing mechanisms, with an emphasis on in vitro validation in living cells. Proposals should demonstrate the ability to design novel writing or erasing mechanisms, modify the epigenome of living cells, and detect targeted base modifications. Key areas of interest include nucleic acid chemistry, protein engineering, and synthetic biology. The submission process involves an abstract due by May 27th, 2026, followed by invited oral proposal packages, with an accelerated award option available. This initiative aims to expand epigenetic editing platforms beyond current limitations, addressing challenges like cellular compatibility and the need for new writer and eraser proteins.