Physics-Based Control Over de novo Synthesis of DNA or RNA

Background
The Defense Advanced Research Projects Agency (DARPA) Biological Technologies Office (BTO) aims to enhance understanding of biotechnological advancements that could facilitate the synthesis of de novo DNA and RNA sequences in vivo.

This initiative is driven by the potential of synthetic DNA and RNA to address global challenges in rapid prototyping, genetic engineering, and biopharmaceuticals. Traditional methods for synthesizing these sequences face limitations related to size, complexity, scalability, and environmental concerns, necessitating alternative biocatalytic approaches.

Work Details
This Request for Information (RFI) seeks insights into the development of a platform for in vivo synthesis of DNA/RNA where sequences are defined by physical stimulation rather than template strands. Key areas of focus include:
1. **Initiation**: Strategies for activating and synchronizing initiation processes across multiple synthase units using physical stimuli.
2. **Elongation**: Approaches for controlling nucleotide incorporation with precision during elongation using light or other stimuli; exploring the use of chimeric or non-traditional enzymes for this process.
3. **Termination**: Methods for controlling transcription termination with physical stimuli and ensuring post-synthesis modifications for functional protein production.
4. **State of Art**: Evaluating current methods for DNA/RNA synthesis and identifying improvements that could be achieved through an enzymatic platform utilizing physical stimuli.
5. **Biosecurity**: Addressing security vulnerabilities associated with engineered nucleic acid synthesis and proposing guidelines for monitoring risks.

Period of Performance
Responses are due by March 20th, 2025, with potential follow-up activities including a workshop on May 1st, 2025.

Place of Performance
The workshop may be held in Arlington, VA.