CRISPR/Cas is a highly specific and efficient DNA/RNA sensing and cleavage system, which has become a breakthrough technology in gene editing and biosensing. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, i.e. the code that tells the nucleotide-enzyme system where and when to act. While the Cas enzymes (CRISPR associated enzymes) are the biological tools that realize the targeted cleavage in oligonucleotides. Though the investment in CRISPR/Cas has exploded, there are still large gaps in the central knowledge base. While CRISPR/Cas in an amazing tool for new science, it has also been recognized as a possible biothreat (Worldwide Threat Assessment of the US Intelligence Community (2016): WEAPONS OF MASS DESTRUCTION), making thorough understanding of the system a strategic need. One area where NRL has the proper expertise to generate deeper understanding and obtain design principals is in the interface of CRISPR/Cas with nanoparticles (NPs) and 2-D surfaces. This program combines DNA nanotechnology and surface functionalization to further the fundamental understanding of CRISPR/Cas activity when the enzyme or substrate is conjugated to NP and 2-D surfaces. Success will improve CRISPR/Cas activity when surface bound, a key development for optimal sensing approaches, as well as developing safer more precise genome editing systems.

Example work: 

Christopher M. Green, Joseph Spangler, Kimihiro Susumu, David A. Stenger, Igor L. Medintz, and Sebastián A. Díaz, “Quantum Dot-Based Molecular Beacons for Quantitative Detection of Nucleic Acids with CRISPR/Cas(N) Nucleases” ACS Nano, 2022, 16, (12), 20693-20704, DOI: 10.1021/acsnano.2c07749