DURIP Combinatorial nucleic acid nanoparticle libraries for materials research and molecular catalysis
Abstract
PROJECT ABSTRACT # Kristy Hentchel, Office of Naval Research This abstract is publicly releasable. The scaffolded DNA origami method allows for the fabrication of nucleic acid nanoparticles (NANPs) with nanoscale control over the size and geometry of the NANP as well as the positioning of secondary molecules. This state-of-the-art materials technology has enabled numerous transformative applications in disparate impactful research directions such as structural biology, therapeutic delivery, light harvesting, quantum sensing and computing, and molecular computing and data storage. To enable the rapid design of DNA- and RNA-based nanoparticles for theseapplications, our lab has developed several top-down computational algorithms (DAEDALUS, PERDIX, TALOS, METIS, pyDAEDALUS, ATHENA) that offer the ability to generate nearly arbitrary two- and three-dimensional nanoparticles. We have also developed in-house enzymatic and biotechnological approaches to synthesize single-stranded DNA and RNA scaffolds with custom length and sequence at scales for in vivo delivery. Additionally, we have developed chemical functionalization techniques to position diverse molecules onto NANPs with nanoscale precision. With design and fabrication bottlenecks overcome, we are now pursuing the generation of large libraries of NANPs in diverse applications that utilize the design-fabricate-characterize-test materials design cycle. To valorize the process ofNANP materials library generation with diverse structural and chemical properties, here we seek to acquire high-throughput characterization and testing equipment which remain limited in our current synthesis laboratory. The materials design cycle requires multiplexed characterization techniques to ensure robust and reproducible fabrication protocols, and the subsequent testing of libraries inbespoke assays, all in a high-throughput, automated manner to enable the accurate analysis of large NANP libraries. The equipment we propose acquiring will automate remaining manual steps in our workflow and increase the throughput of bottlenecks within the workflow, both of which will valorize our NANP materials library capabilities. These will complement our current automated, high-throughput liquid handling equipment (LabCyte Echo 555, Formulatrix FLO I8, Biotek EL406) and our high-throughput characterization equipment(Tecan Spark). We propose acquiring a Qiagen QIAxcel Connect capillary electrophoretic instrument to replace our low-throughput andmanual gel electrophoresis equipment, a Peak Genius XE35 nitrogen generator to allow for continuous operation of our LC/MS for nucleic acid characterization, and a set of Integra Mini 96 liquid handlers to fill in the gaps of liquid handling requirements in testing NANP libraries. This set of equipment would enable our long-term goals in generating libraries of nucleic acid-based nanoparticles for multiple applications currently funded by the ARO, ONR, DoE, NIH, and NSF. We will continue to make these high-throughput capabilities accessible to the MIT Biological Engineering Department Teaching Laboratory to facilitate undergraduate and graduate education in nucleic acid nanotechnology.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 15, 2024
- Source ID
- N000142412254
Entities
People
- Mark Bathe
Organizations
- Massachusetts Institute of Technology
- Office of Naval Research
- United States Navy