Single Molecule studies of CRISPR/Cas9 activities during
Lead Research Organisation:
Imperial College London
Department Name: Dept of Medicine
Abstract
Currently my research interests lie firmly within exploring the nucleus. The majority of my
experience is working on the mechanism of DNA damage and repair.
experience is working on the mechanism of DNA damage and repair.
People |
ORCID iD |
| David Rueda (Primary Supervisor) | |
| Matt Newton (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/P504889/1 | 03/10/2016 | 02/04/2021 | |||
| 1811934 | Studentship | BB/P504889/1 | 01/10/2016 | 30/09/2020 | Matt Newton |
| Description | The recently discovered CRISPR-Cas9 technology has the potential to be used to perform gene editing in humans and correct faulty genes for the treatment of genetic diseases. There are concerns however about unexpected editing at genes that are not the intended target. We have demonstrated that stretching DNA can induce more of these 'off-target' effects and suggest that processes in cell which effectively stretch DNA could be responsible for causing some of these unwanted edits when CRISPR-Cas9 is used to edit genes. We hypothesised that the reason DNA stretching induces off-targets is that it destabilises the structure of DNA, allowing the two stands which are bound together to form the double-helix to be easily separated. Other cellular processes also destabilise the DNA structure such as negative supercoiling, when the DNA helix is partially untwisted. This can occur during expression of genes and when the DNA is being replicated. Using multiple techniques we how now also demonstrated that negative supercoiling does indeed induce off-target activity of Cas9. This supports our hypothesis that off-targeting is induced by process which destabilise the DNA structure. |
| Exploitation Route | Our findings add to our understanding of the mechanism of how CRISPR-Cas9 act to edit genes at the correct and incorrect sites - this can inform the design of safer and more efficient CRISPR-Cas9 gene editing techniques. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| URL | https://lms.mrc.ac.uk/the-promiscuity-of-cas9-do-we-need-a-gene-editing-revolution/ |
| Description | PubHD Talk |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | Outreach event where PhD Students present their work in the form of an informal 10 min talk suitable for a lay audience followed by 20 min questions and discussion. Approximately 30 people attended many of whom where other London based PhD students but also some general public. The talk focused on the topic of gene editing in light of the resent news of two 'CRISPR Babies' the first genetically edited babies to be born. During the 20 min questions there was interesting debate about the ethics and pro/cons of human gene editing. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.facebook.com/events/642633162819123/ |