| EPSRC Reference: |
EP/S019944/1 |
| Title: |
CRISPR Chemistry |
| Principal Investigator: |
Brown, Professor T |
| Other Investigators: |
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| Researcher Co-Investigators: |
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| Project Partners: |
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| Department: |
Oxford Chemistry |
| Organisation: |
University of Oxford |
| Scheme: |
Standard Research |
| Starts: |
16 April 2019 |
Ends: |
30 September 2021 |
Value (£): |
254,184
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| EPSRC Research Topic Classifications: |
| Biological & Medicinal Chem. |
Biophysics |
| Chemical Biology |
Chemical Synthetic Methodology |
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| EPSRC Industrial Sector Classifications: |
| No relevance to Underpinning Sectors |
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| Related Grants: |
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| Panel History: |
| Panel Date | Panel Name | Outcome |
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05 Dec 2018
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EPSRC Physical Sciences - December 2018
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Announced
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Summary on Grant Application Form |
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A transformative new technology for gene editing, known as CRISPR-Cas, was recently discovered. It allows a protein (Cas9) to be programmed by a CRISPR RNA molecule to modify specific sequences in genomic DNA. This can be used to alter the levels of specific proteins in cells, and can even be used to eliminate them or change their function (via site-specific mutation). This technology has profound implications in many areas of biology and medicine and, in the future, could be used to successfully treat human genetic diseases and cancer. By creating artificial (modified) Cas9 proteins, it is also possible to edit the cell's RNA molecules and to create detailed images of the genome in live cells in real-time. However, there are drawbacks to CRISPR-Cas technology: the number of CRISPR RNA molecules needed to perform some editing tasks is cost-prohibitive, imaging multiple DNA loci in the genome is difficult, and to completely change a cell's characteristics (cell type) is not currently feasible. Moreover, unintended editing events in the genome (off-target effects) are common and these are potentially catastrophic, particularly in the therapeutic arena where they could cause cancer when used in therapeutic applications. We will address these problems by chemically modifying the Cas9-binding CRISPR RNA molecule in various ways. Libraries of RNA molecules will be created by mixing and matching (chemically ligating) the short variable gene-targeting RNA moiety with a larger invariable RNA sequence needed for association with Cas9 protein. By adding fluorescent dyes to these RNA molecules and developing systems that intelligently activate and programme the output colour, live-cell imaging capabilities will be significantly improved. In order to control a cell's behaviour, we will append short pieces of DNA to the CRISPR RNA molecule that will recruit key gene regulating proteins within the cell and enable us to fine-tune gene expression. Finally, the use of light-activated chemically modified Cas9-binding RNA molecules, which can only transiently and subtly damage DNA, will be investigated to reduce undesirable off-target effects. These nucleic acid chemistry-driven objectives are aimed at facilitating research that would otherwise be impractical or impossible using current Cas9 technology and in the long term could enable exciting new applications.
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Key Findings |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Potential use in non-academic contexts |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Impacts |
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| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
| Summary |
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| Date Materialised |
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Sectors submitted by the Researcher |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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| Project URL: |
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| Further Information: |
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| Organisation Website: |
http://www.ox.ac.uk |