Synthetic Nucleic Acid Nanoparticles for RNA Structural & Synthetic Biology
Abstract
Nanometer-scale precision engineering can uniquely be accomplished by programmed self- assembly of nucleic acids into complex structures, offering the opportunity to organize secondary molecules including enzymes, peptides, and RNAs in 3D configurations for diverse nanotechnology and structural biology applications. Target applications of relevance to the ONR and warfighter performance include scaffolding multi-enzyme cascades for biosynthesis and biofuels, real-time pathogen detection, molecular computing and memory, and self-assembly, replication, and evolution of nanostructured systems for materials to accommodate environmental shifts. In the next funding cycle of this research grant we seek to continue our work on enabling DNA- and RNA-based scaffolded origami nanoparticle libraries for the 3D capture and coordination of catalytic and active RNAs. Specifically, top-down design of arbitrary 2D and 3D structured DNA-based assemblies has been realized by new algorithms developed in the Bathe lab, which have been validated structurally by the Chiu lab. Further, we have recently developed a new variant of our design algorithm that allows precise structuring of RNA with similar nanoscale engineering capabilities as DNA based on wireframe designs. In the previous funding cycle, we demonstrated 3D capture and coordination of synthetic RNA using structured DNA nanoparticles to enable their high-resolution 3D reconstruction using cryogenic electron microscopy (cryoEM). Leveraging new nanofluidics resources in our lab, including a high-throughput acoustic liquid handling robot, we propose to automate this workflow to aid in the large-scale assembly of computationally generated DNA and RNA nanoparticle libraries to facilitate the 3D capture and coordination of arbitrary RNAs for application to RNA structural and synthetic biology. APPROVED FOR PUBLIC RELEASE.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Feb 17, 2020
- Source ID
- N000142012084
Entities
People
- Mark Bathe
Organizations
- Massachusetts Institute of Technology
- Office of Naval Research
- United States Navy