Structure and mechanisms of RNA-targeting by CRISPR-Cas13a

Project: Research

Project Details

Project Description

This proposal aims to investigate unique structures and mechanisms of CRISPR-Cas13a relevant to its clinical translation into a programmable tool for RNA detection and diagnostics. The overarching goal of the proposed research is to provide the molecular detail necessary for the successful translation of Cas13a into a tractable tool for RNA virus detection and diagnostics. Cas13a is the archetypal RNA-targeting CRISPR-Cas system with the greatest potential for development as an inexpensive and accurate diagnostic. Our integrated approach combining structural biology, biochemistry, and high-throughput library-based RNAseq will catalyze the development of Cas13a-based diagnostics for human-infective RNA viruses.
Short titleCRISPR-Cas13a mechanism
AcronymCas13
StatusActive
Effective start/end date1/01/2031/12/24

Keywords

  • CRISPR
  • viral RNA detection
  • protein structure and function
  • diagnostics
  • Accelerated RNA detection using tandem CRISPR nucleases

    Liu, T. Y., Knott, G. J., Smock, D. C. J., Desmarais, J. J., Son, S., Bhuiya, A., Jakhanwal, S., Prywes, N., Agrawal, S., Díaz de León Derby, M., Switz, N. A., Armstrong, M., Harris, A. R., Charles, E. J., Thornton, B. W., Fozouni, P., Shu, J., Stephens, S. I., Kumar, G. R., Zhao, C. & 15 others, Mok, A., Iavarone, A. T., Escajeda, A. M., McIntosh, R., Kim, S., Dugan, E. J., IGI Testing Consortium, Pollard, K. S., Tan, M. X., Ott, M., Fletcher, D. A., Lareau, L. F., Hsu, P. D., Savage, D. F. & Doudna, J. A., Sep 2021, In: Nature Chemical Biology. 17, 9, p. 982-988 7 p.

    Research output: Contribution to journalArticleResearchpeer-review

    Open Access
    17 Citations (Scopus)
  • Amplification-free detection of SARS-CoV-2 with CRISPR-Cas13a and mobile phone microscopy

    Fozouni, P., Son, S., Díaz de León Derby, M., Knott, G. J., Gray, C. N., D'Ambrosio, M. V., Zhao, C., Switz, N. A., Kumar, G. R., Stephens, S. I., Boehm, D., Tsou, C. L., Shu, J., Bhuiya, A., Armstrong, M., Harris, A. R., Chen, P. Y., Osterloh, J. M., Meyer-Franke, A., Joehnk, B. & 12 others, Walcott, K., Sil, A., Langelier, C., Pollard, K. S., Crawford, E. D., Puschnik, A. S., Phelps, M., Kistler, A., DeRisi, J. L., Doudna, J. A., Fletcher, D. A. & Ott, M., 21 Jan 2021, In: Cell. 184, 2, p. 323-333.e9 20 p.

    Research output: Contribution to journalArticleResearchpeer-review

    Open Access
    167 Citations (Scopus)