New Invention: Control of CRISPR gene editing

30 April 2019

The recent development of gene editing using biological system CRISPR, creates the prospect of dramatic developments in medicine for gene repair and cancer therapy. The CRISPR/Cas9 system allows targeted DNA cleavage and hence editing of the genome. However, unwanted DNA cuts, resulting from non-specific delivery to off-target cells, could promote tumorigenesis. Cell-specific activation of CRISPR/Cas9 is essential to avoid this problem.

Researchers at the University of Oxford have developed a control system that allows spatio-temporal activation of CRISPR, based on an engineered RNA guide strand. This technology is modular, so both targeting and sensing can be adapted to allow new genes to be targeted, subject to the detection of new biomolecular triggers. It also provides a platform technology that can be applied to any gene therapy based on RNA-dependent nucleases such as Cas9.

CRISPR/Cas9 approaches and limitations

CRISPR is described as “the technology of the century” and brings the hope of treatments for currently incurable diseases, by excising or silencing genes that drive tumour proliferation, repair of faulty genes, or by killing diseased cells.

However, unwanted DNA cuts, resulting from non-specific delivery to off-target cells, remain a serious problem in the successful clinical translation of CRISPR-based therapeutics. Exact spatio-temporal control of CRISPR/Cas9 activity would lead to the development of new therapies and new tools for biotechnology with great translational potential.

Improvement of current methods with the Oxford technology

Oxford academics have developed an innovative control system allowing gene editing to be activated only in response to precisely defined combinations of biomolecular signals in targeted cell populations.

This technology is based on engineered Cas9 guide strands that incorporate sensor motifs that allow the nuclease Cas9 to cut DNA only when conditions characteristic of target cells are met. By improving the CRISPR/Cas9 constructs with the use of this modified guide-RNAs (gRNA) containing the blocking module, a nucleic-acid dependent activation of the Cas9 enzyme is allowed.
Furthermore, this unique design provides Cas9 sensing abilities with minimal leakage of activity, which is desirable for precise enzyme activity.

Several RNA guide strands have already been developed in the laboratory. Efficiency and selectivity of the system have been successfully tested in vitro and in cellular models.

Main applications of conditional regulation

This new approach improves the current CRISPR/Cas9 gene editing applications and it can be applied to any gene regulation technique but with improved implementation and results:

  • Use in biomedical applications for cell-type specific activation of the CRISPR/Cas9 system
  • Tool for synthetic biology: genetic circuits or nucleic-acid nanotechnology
  • Production of other conditionally activated CRISPR/Cas9 systems based on the use of other activation molecules, such as proteins or small molecules


This technology is subject to a patent application. Oxford University Innovation is interested in hearing from companies that would like to license this technology.