Developing an initiative in stem cell editing for human genetic diseases.
Lead Research Organisation:
University of Oxford
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
The recent development of genome editing using programmable nucleases has already transformed our ability to perform experiments in mammalian cells rapidly, at high throughput and with high precision. The next challenge is to apply this discovery to precisely edit and correct genetic defects in human stem cells in a new approach to the treatment of inherited diseases. In this proposal we aim to address the key preclinical hurdles in achieving this by editing haematopoietic stem cells from patients with severe haemoglobinopathies, with the goal of rapidly progressing this knowledge to early phase clinical trials.
Using flexible funding allocated to the University as a block grant, we will facilitate the development of this new initiative bringing together the considerable expertise and technical know-how in a wide range of interdisciplinary groups to address this focussed problem. We anticipate that genome editing will ultimately find application in a wide range of human diseases and the University of Oxford is fully committed to support its early development in blood diseases to establish the principles of this approach and the longer term application of this exciting new technology to a broad range of challenges in clinical medicine.
Using flexible funding allocated to the University as a block grant, we will facilitate the development of this new initiative bringing together the considerable expertise and technical know-how in a wide range of interdisciplinary groups to address this focussed problem. We anticipate that genome editing will ultimately find application in a wide range of human diseases and the University of Oxford is fully committed to support its early development in blood diseases to establish the principles of this approach and the longer term application of this exciting new technology to a broad range of challenges in clinical medicine.
People |
ORCID iD |
Publications
Babbs C
(2020)
Variable cells with identical genetic codes.
in Blood
Badat M
(2017)
Gene Therapy in a Patient with Sickle Cell Disease.
in The New England journal of medicine
Badat M
(2023)
Direct correction of haemoglobin E ß-thalassaemia using base editors
in Nature Communications
Blobel GA
(2021)
Testing the super-enhancer concept.
in Nature reviews. Genetics
Broderick R
(2016)
EXD2 promotes homologous recombination by facilitating DNA end resection.
in Nature cell biology
Brown J
(2018)
A tissue-specific self-interacting chromatin domain forms independently of enhancer-promoter interactions
in Nature Communications
Chiariello A
(2020)
A Dynamic Folded Hairpin Conformation Is Associated with a-Globin Activation in Erythroid Cells
in Cell Reports
Description | BRC3 Haematology and Stem Cell |
Amount | £4,602,645 (GBP) |
Funding ID | BRC3 |
Organisation | National Institute for Health Research |
Department | NIHR Biomedical Research Centre |
Sector | Public |
Country | United Kingdom |
Start | 04/2017 |
End | 03/2022 |
Description | Detection of mutations to allow safe gene editing and transplantation of haemopoietic cells |
Amount | £1,040,932 (GBP) |
Funding ID | MR/R008108/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 02/2018 |
End | 02/2022 |
Description | Developing a programme for stem cell editing for human blood diseases |
Amount | £173,793 (GBP) |
Organisation | University of Oxford |
Department | John Fell Fund |
Sector | Academic/University |
Country | United Kingdom |
Start | 01/2016 |
End | 12/2016 |
Description | Development of a novel therapy for beta thalassaemia using CRISPR/Cas9 to edit the major alpha globin enhancer |
Amount | £253,742 (GBP) |
Funding ID | MR/P019633/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2017 |
End | 09/2020 |
Description | Exploring mechanisms of enhancer action in erythropoiesis |
Amount | £250,000 (GBP) |
Funding ID | 209181 |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 04/2018 |
End | 03/2022 |
Description | Identifying suppressor mutations of ATR-X and ADNP syndromes using a novel CRISPR-based screening method in mice |
Amount | £250,000 (GBP) |
Funding ID | 210913 |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 11/2018 |
End | 10/2022 |
Description | The Oxford Single Cell Biology Consortium |
Amount | £399,179 (GBP) |
Funding ID | MR/M00919X/1 |
Organisation | University of Oxford |
Department | John Fell Fund |
Sector | Academic/University |
Country | United Kingdom |
Start | 05/2016 |
End | 03/2019 |
Description | WIMM - MRC Festival Establishment Award |
Amount | £3,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 02/2019 |
End | 03/2024 |
Description | WIMM - WIMM MHU Capital Funding Award 2019/20 |
Amount | £85,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 04/2019 |
End | 03/2020 |
Description | Enhancing tumour specific immune responses for the treatment of ovarian cancer |
Organisation | University of Oxford |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Access to ovarian cancer biology and computational work |
Collaborator Contribution | Immunology expertise and cancer antigene prediction. |
Impact | The Ovarian Cancer Action (OCA) international grand challenge award Publication by Cancer Cell in Feb 2020: " The Repertoire of Serous Ovarian Cancer Non-genetic Heterogeneity Revealed by Single-Cell Sequencing of Normal Fallopian Tube Epithelial Cells" |
Start Year | 2016 |
Title | METHOD OF ANALYSING DNA SEQUENCES |
Description | The present invention relates to a method of identifying nucleic acid regions within a nucleic acid sample which interact with one another. In particular, the method relates to a chromatin conformation capture (3C) method which may be used to analyse the interactions between enhancers, silencers, boundary elements and promoters at individual loci at high resolution. |
IP Reference | WO2017068379 |
Protection | Patent application published |
Year Protection Granted | 2017 |
Licensed | No |
Impact | None so far |
Description | 11th Cooley's Anemia Meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited talk in which I presented recent research from the laboratory following and introduction providing background to the field of interest. The attendance included students, junior research staff and senior scientists. |
Year(s) Of Engagement Activity | 2022 |
Description | David & Jean Nathan Inaugural Lecture |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited talk in which I presented recent research from the laboratory following and introduction providing background to the field of interest. The attendance included students, junior research staff and senior scientists. |
Year(s) Of Engagement Activity | 2022 |
Description | EBMT Haemoglobinopathy Meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited talk in which I presented recent research from the laboratory following and introduction providing background to the field of interest. The attendance included students, junior research staff and senior scientists. |
Year(s) Of Engagement Activity | 2022 |
Description | European School of Haematology |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited talk in which I presented recent research from the laboratory following and introduction providing background to the field of interest. The attendance included students, junior research staff and senior scientists. |
Year(s) Of Engagement Activity | 2023 |
Description | MPI Berlin |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited talk in which I presented recent research from the laboratory following and introduction providing background to the field of interest. The attendance included students, junior research staff and senior scientists. |
Year(s) Of Engagement Activity | 2023 |
Description | Molecular Haematology Unit seminar |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | A talk regarding the work on single-cell systems biology carried out by the company to date. This sparked a good debate between the presenter and the audience. |
Year(s) Of Engagement Activity | 2016,2017,2018,2019 |
Description | Oxford TEE meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Postgraduate students |
Results and Impact | Invited talk in which I presented recent research from the laboratory following and introduction providing background to the field of interest. The attendance included students, junior research staff and senior scientists. |
Year(s) Of Engagement Activity | 2022 |
Description | Royal Society Summer Exhibition |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | The presentation was part of the Royal Society Summer Exhibition attended by schoolchildren, members of the public and members of the scientific community. This exhibition is probably the largest of the year in terms of attendees over the course of a week. |
Year(s) Of Engagement Activity | 2017 |
Description | Science Career Seminar |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Postgraduate students |
Results and Impact | A career talk to students and post-docs involving working in the USA |
Year(s) Of Engagement Activity | 2016 |
Description | Spetses Summer School |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited talk in which I presented recent research from the laboratory following and introduction providing background to the field of interest. The attendance included students, junior research staff and senior scientists. |
Year(s) Of Engagement Activity | 2022 |
Description | Switching Conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited talk in which I presented recent research from the laboratory following and introduction providing background to the field of interest. The attendance included students, junior research staff and senior scientists. |
Year(s) Of Engagement Activity | 2022 |
Description | Symposium on Chromatin Changes |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited talk in which I presented recent research from the laboratory following and introduction providing background to the field of interest. The attendance included students, junior research staff and senior scientists. |
Year(s) Of Engagement Activity | 2022 |