FY19 ANNUAL REPORT
Controlling the activity of gene-editing tools. Sandia developed a pipeline to discover clinically useful CRISPR-Cas9 genome-editing inhibitors to ensure the safety of CRISPR-based gene therapies and provide an antidote in the event of unwanted exposure. In collaboration with the University of California, Berkeley, a high- throughput fluorescence resonance energy transfer (FRET)-based assay was developed with low background noise and high sensitivity. A phage display assay was also developed to identify small peptides with high affinity binding to Cas9, and has identified peptides that selectively block SpyCas9 activity and peptides with activity across Cas9 variants. This represents the first identification of broad-spectrum anti-CRISPR therapeutics that block multiple Cas9 variants from phylogenetically CRISPR-Cas systems. Novel zoned wasteforms for high-priority radionuclide waste streams. A new negative thermal expansion (NTF) material, that readily incorporates radionuclides of interest, including Pu and Tc, was discovered and characterized in the process of synthesizing a phase-pure Zr 2 P 2 WO 12 . The project successfully showed that NTF materials that shrink upon amorphization are viable wasteforms. Because of their resistance to long- term radiation damage, these materials can maintain radionuclide isolation more effectively than standard wasteforms, and may represent ideal solutions to prevent remobilization of radionuclides. Nuclear Fusion Award Sandia Fellow Keith Matzen received the 2019 Distinguished Career Award from Fusion Power Associates , a national nonprofit research and education foundation, for his many contributions to the Labs’ development of nuclear fusion. The foundation annually brings together senior U.S. and international fusion experts to review the status of fusion research and consider ways to move forward. The goal is to provide timely information on the status of fusion development and other applications of plasma science. Keith views this particular award as a recognition of the large team of people who made tremendous progress on many very difficult problems during his time as senior manager and director in the Pulsed Power Sciences Center. Within this context, LDRD investments had a large impact on the overall success of the program.
LABORATORY DIRECTED RESEARCH & DEVELOPMENT
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