SEP 30, 2020 1:30 PM PDT

Harnessing novel CRISPR systems for genome engineering

Presented at: CRISPR 2020
C.E. Credits: P.A.C.E. CE Florida CE
Speakers
  • Fellow, McGovern Institute for Brain Research at MIT
    Biography

      Omar Abudayyeh, Ph.D., is a McGovern Institute Fellow at the Massachusetts Institute of Technology where he leads a lab on exploring microbial diversity for new biotechnological tools related to genome editing and gene delivery. He previously was at Harvard Medical School and the Harvard-MIT Health Sciences and Technology program as a graduate student. He completed his doctoral work in Feng Zhang's lab at the Broad Institute of MIT and Harvard, where his research centered on novel CRISPR enzymes for applications in genome editing, therapeutics, and diagnostics. Dr. Abudayyeh's work focused on uncovering novel CRISPR enzymes beyond Cas9 for biotechnological applications. He co-led the discovery and characterization of multiple landmark pieces of work, including the characterization of Cpf1 for novel genome editing applications and the first single-protein RNA-guided RNA-targeting enzyme C2c2/Cas13. His follow-up work on C2c2/Cas13 biology led to the development of SHERLOCK technology, and a new set of tools for precise editing of transcripts and visualizing them in mammalian cells with potential for RNA therapeutics. In recognition of his technology developments, Dr. Abudayyeh was recognized as 2018 Forbes 30 under 30 in Science and Health Care and Business Insider 30 under 30. Dr. Abudayyeh graduated from MIT in 2012 with a B.S. in mechanical engineering and biological engineering, where he was a Henry Ford II Scholar and a Barry M. Goldwater Scholar.

    • Fellow, McGovern Institute
      Biography

        Jonathan Gootenberg, Ph.D. draws from fundamental microbiology to engineer new molecular tools. These tools, including the popular genome editing system CRISPR, allow for unprecedented manipulation and profiling of cellular states in the body, and have multiple applications in basic science, diagnostics, and therapeutics. Dr. Gootenberg uses gene editing, gene delivery, and cellular profiling methods to understand the changes that occur in the brain and other organs during aging, with the goal of generating new therapies for degenerative disease. Dr. Gootenberg earned his bachelor's degree in mathematics and biological engineering at MIT and received his PhD in Systems Biology from Harvard University, during which he conducted research with Aviv Regev and Feng Zhang at the McGovern Institute and Broad Institute of MIT and Harvard. During his graduate work, Gootenberg focused on the development of molecular technologies for treating and sensing disease states, crossing disciplines by utilizing novel computational techniques, microbiology, biochemistry, and molecular biology to uncover new CRISPR tools, including Cas12 and Cas13. He and his co-authors developed Cas13 into a toolbox with uses in fundamental research, therapeutics, and diagnostics. These applications include RNA knockdown, imaging, the base editing platform REPAIR, and the sensitive, specific, and portable diagnostic platform SHERLOCK. He is one of the first members of the McGovern Institute Fellows program, which supports the transition to independent research for exceptional recent PhD graduates.


      Abstract

      RNA plays important and diverse roles in biology, but molecular tools to manipulate and measure RNA are limited. We demonstrate that RNA-targeting CRISPR effector Cas13 can be engineered for RNA diagnostics and mammalian cell RNA knockdown, binding, and editing. We demonstrate diagnostic applications of Cas13 for rapid and sensitive COVID-19 diagnostics. We also show Cas13 can be heterologously expressed in mammalian and plant cells for targeted knockdown of either reporter or endogenous transcripts, targeted RNA binding for transcript imaging, and programmable RNA editing. We develop engineered Cas13-based RNA editing tools for A-to-I and C-to-U base editing and show applications of these tools for therapeutics. Our results establish CRISPR-Cas13 as a flexible platform for RNA targeting with wide applicability for studying RNA or therapeutics.

      Learning Objectives:

      1. Learn about the discovery of Cas13 and its function as a programmable RNA-targeting CRISPR enzyme

      2. Learn about how Cas13 can be engineered for nucleic acid diagnostics and for rapid, cheap, and sensitive COVID-19 detection

      3. Learn about how Cas13 can be engineered for programmable RNA editing and therapeutic applications


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