Development of highly sensitive methods for defining off target mutations to enable safe gene editing of haematopoietic cells for transplantation
Lead Research Organisation:
University of Oxford
Department Name: Weatherall Inst of Molecular Medicine
Abstract
RNA guided endonucleases (RGENs), such as the CRISPR-Cas9 system have revolutionised our ability to edit the genome because they allow us to cut and edit the genome at the sequence defined by a RNA guide, which can be rapidly designed and manufactured. This has had a huge impact on molecular biology; allowing the genome of a wide variety of different cell types and organisms to be edited. The next challenge is to use this technology to edit the genome of human cells to treat disease. Haematopoiesis is one of the first areas in which this technology will be successfully implemented in the clinic because haematopoietic stem cell (HSC) transplantation has been performed for over 40 years and facilities for collecting, purifying and transplanting human HSCs are well established.
One of the major barriers to using genome editing technology in patients is the potential risk of malignant transformation from unintended mutations during the editing process. In order to improve genome editing techniques to the point at which they can be safely used in human trials it is critical that assays are developed to define mutations in primary cells that have undergone genome editing. These off target effects need to be defined accurately in an unbiased genome wide fashion and the assays need to be highly sensitive so that rare off target mutations can be detected because malignancy arises from clonal transformation of single cells. To date, several methods have been described for determining off target effects but none of the techniques is able to define mutations sensitively and accurately in primary cells. This is a key stumbling block to the clinical application of these techniques because without rapid and cost effective methods to compare the accuracy of the huge variety of different techniques available for genome editing it will be difficult to develop safe methods of editing for use in human trials.
I will develop a novel method that initially identifies all potential sites of in vitro RGEN in naked DNA (this has previously been shown to be a highly predictive of potential sites of off target activity). Subsequently these sites will be sequenced at great depth using biotinylated oligonucleotides designed to capture DNA at the target sites identified in vitro. Using this it should be relatively straightforward to make the assay is at least 100 times more sensitive than the best available methods. I will also use this approach to look for rare sites of unintended insertion of viral vectors and template sequences.
The overall burden of mutations that occur during the editing process will also be investigated. This will be done by performing whole genome sequencing on haematopoietic stem and progenitor cells purified by flow cytometry both before and after the editing process. Methods will be used to minimise sequencing errors and software will be written to define the overall burden of mutations from the variability of the sequences derived from sequencing.
These methods will be used to optimise two models of genome editing for the treatment of thalassaemia and sickle cell disease for potential clinical use. First a model has been developed in the host laboratory which aims to cure patients with transfusion dependent HbE beta thalassaemia, which accounts for around 50% of transfusion dependent thalassaemia, by deleting key transcription factor binding sites at the alpha globin gene. In addition an established method will be set up, which uses an RGEN to insert a DNA template to correct the beta globin gene in situ and simultaneously express a cell surface marker that allows purification of corrected cells. This will allow me to test the methods for quantification of off target effects on the two main strategies for using RGENs for editing cells.
One of the major barriers to using genome editing technology in patients is the potential risk of malignant transformation from unintended mutations during the editing process. In order to improve genome editing techniques to the point at which they can be safely used in human trials it is critical that assays are developed to define mutations in primary cells that have undergone genome editing. These off target effects need to be defined accurately in an unbiased genome wide fashion and the assays need to be highly sensitive so that rare off target mutations can be detected because malignancy arises from clonal transformation of single cells. To date, several methods have been described for determining off target effects but none of the techniques is able to define mutations sensitively and accurately in primary cells. This is a key stumbling block to the clinical application of these techniques because without rapid and cost effective methods to compare the accuracy of the huge variety of different techniques available for genome editing it will be difficult to develop safe methods of editing for use in human trials.
I will develop a novel method that initially identifies all potential sites of in vitro RGEN in naked DNA (this has previously been shown to be a highly predictive of potential sites of off target activity). Subsequently these sites will be sequenced at great depth using biotinylated oligonucleotides designed to capture DNA at the target sites identified in vitro. Using this it should be relatively straightforward to make the assay is at least 100 times more sensitive than the best available methods. I will also use this approach to look for rare sites of unintended insertion of viral vectors and template sequences.
The overall burden of mutations that occur during the editing process will also be investigated. This will be done by performing whole genome sequencing on haematopoietic stem and progenitor cells purified by flow cytometry both before and after the editing process. Methods will be used to minimise sequencing errors and software will be written to define the overall burden of mutations from the variability of the sequences derived from sequencing.
These methods will be used to optimise two models of genome editing for the treatment of thalassaemia and sickle cell disease for potential clinical use. First a model has been developed in the host laboratory which aims to cure patients with transfusion dependent HbE beta thalassaemia, which accounts for around 50% of transfusion dependent thalassaemia, by deleting key transcription factor binding sites at the alpha globin gene. In addition an established method will be set up, which uses an RGEN to insert a DNA template to correct the beta globin gene in situ and simultaneously express a cell surface marker that allows purification of corrected cells. This will allow me to test the methods for quantification of off target effects on the two main strategies for using RGENs for editing cells.
Technical Summary
Sites of off target CRISPR-Cas9 nuclease activity will initially be defined in purified genomic DNA. Digenome-seq shows that RGEN cleavage in vitro is a good predictor of off target sites but it uses whole genome sequencing to identify cut sites, making it prohibitively expensive and insensitive. The novel method involves ligating a customized sequencing adaptor to RGEN cut sites to allow them to be specifically sequenced.
I have previously developed oligonucleotide capture technology for extremely deep sequencing (>100,000 fold coverage). Biotinylated oligonucleotides will be designed to pull down all of the potential sites of Cas9 cleavage identified in vitro and these will then be used to define with high sensitivity whether off target mutations occur during in vivo editing of primary cells. In addition oligonucleotides will be designed to the viral vector and the sequences to be inserted by HDR so that off target sits of integration can be identified. I plan to investigate whether a chromosome conformation capture based method (Capture-C) I pioneered, can improve the sensitivity of the assay detect to sites of off target integration.
Off target effects will be studied in two models of genome editing for the treatment of thalassaemia and sickle cell disease. The first model has been developed in the host laboratory to treat HbE beta thalassemia and uses a single CRISPR-Cas9 cut and the non homologous end joining pathway to delete key transcription factor binding sites at the main enhancer of the alpha globin gene. A previously published method will also be set up, which uses homologous recombination to correct the beta globin gene in situ and simultaneously insert a cell surface marker for purification of corrected cells. This uses an adeno-associated virus (AAV) 6 vector to deliver the template for HDR and I plan to use a second AAV-6 vector to deliver Cas9 controlled by an inducible promoter to study how Cas9 expression alters off target effects.
I have previously developed oligonucleotide capture technology for extremely deep sequencing (>100,000 fold coverage). Biotinylated oligonucleotides will be designed to pull down all of the potential sites of Cas9 cleavage identified in vitro and these will then be used to define with high sensitivity whether off target mutations occur during in vivo editing of primary cells. In addition oligonucleotides will be designed to the viral vector and the sequences to be inserted by HDR so that off target sits of integration can be identified. I plan to investigate whether a chromosome conformation capture based method (Capture-C) I pioneered, can improve the sensitivity of the assay detect to sites of off target integration.
Off target effects will be studied in two models of genome editing for the treatment of thalassaemia and sickle cell disease. The first model has been developed in the host laboratory to treat HbE beta thalassemia and uses a single CRISPR-Cas9 cut and the non homologous end joining pathway to delete key transcription factor binding sites at the main enhancer of the alpha globin gene. A previously published method will also be set up, which uses homologous recombination to correct the beta globin gene in situ and simultaneously insert a cell surface marker for purification of corrected cells. This uses an adeno-associated virus (AAV) 6 vector to deliver the template for HDR and I plan to use a second AAV-6 vector to deliver Cas9 controlled by an inducible promoter to study how Cas9 expression alters off target effects.
Planned Impact
The outcomes of this research would be of particular benefit to researchers in the field of genome editing and clinicians in the field of bone marrow transplantation and cellular therapy. However, it has the potential to have a much broader impact. The development of methodology to define off target effects will further our understanding of the potential risks of genome editing and will allow us to develop safe methods for editing the genome of potentially any cell type or organism. Once developed, the methodology will be patented as it is likely that it will be of commercial value. Commercial exploitation of intellectual property will be achieved through the Oxford University Innovation Ltd. licensing and ventures team.
Importantly, I envisage that the work will also lead to a method of quantifying the general mutational burden in haematopoietic stem cells. This could also have a broad impact on current medical practice because it will allow us to define the damage caused by different cytotoxics and chemotherapy regimens to haematopoietic stem cells and the ancillary risk of secondary myelodysplasia.
Development of methods for safe genome editing of haematopoietic stem cells and lymphocytes has potential the to have a therapeutic impact on a very wide range of diseases. It is likely that long term cure for inherited genetic diseases of haematopoiesis, such as sickle cell disease, thalassaemia, Wiskott-Aldrich syndrome and Fanconi anaemia will be achieved within the next decade. At present autologous bone marrow transplantation is becoming an important treatment modality for some autoimmune diseases, in particular multiple sclerosis. Genome editing of autologous haematopoietic stem cells therefore has the potential to provide long term cure for a wide variety of autoimmune conditions. Engineered Chimeric Antigen Receptor (CAR) T cells are currently an important treatment modality for several forms of haematological malignancy including chronic lymphocytic leukaemia and acute lymphoblastic leukaemia. Interestingly, it has recently been demonstrated that targeting of chimeric antigen receptors to the endogenous T cell receptor locus using CRISPR-Cas9 improves the efficiency of CAR T cells. The power of this technology is likely to improve and it is likely to be applicable to a broader range of malignancies in the future. Finally it is also likely that engineered haematopoietic cells will be used to treat infectious diseases. It has been shown that allogeneic transplantation with a CXCR5 negative donor can cure HIV. Although trials of engineered lymphocytes with CXCR5 knockdown were unsuccessful for treating HIV, autologous transplantation with HSCs with knockdown of CXCR5 has the potential to be curative analogous to allogeneic transplantation.
The work to be developed in this project is likely to provide a rapid method to identify mutations resulting from genome editing and this has the potential to allow the field to improve the genome editing technology more rapidly. Since developing genome editing technology is an international effort, the research is likely to have a significant impact on the UK profile in this area. If successful the impact of the research could be very rapid indeed (within 12 months).
Importantly, I envisage that the work will also lead to a method of quantifying the general mutational burden in haematopoietic stem cells. This could also have a broad impact on current medical practice because it will allow us to define the damage caused by different cytotoxics and chemotherapy regimens to haematopoietic stem cells and the ancillary risk of secondary myelodysplasia.
Development of methods for safe genome editing of haematopoietic stem cells and lymphocytes has potential the to have a therapeutic impact on a very wide range of diseases. It is likely that long term cure for inherited genetic diseases of haematopoiesis, such as sickle cell disease, thalassaemia, Wiskott-Aldrich syndrome and Fanconi anaemia will be achieved within the next decade. At present autologous bone marrow transplantation is becoming an important treatment modality for some autoimmune diseases, in particular multiple sclerosis. Genome editing of autologous haematopoietic stem cells therefore has the potential to provide long term cure for a wide variety of autoimmune conditions. Engineered Chimeric Antigen Receptor (CAR) T cells are currently an important treatment modality for several forms of haematological malignancy including chronic lymphocytic leukaemia and acute lymphoblastic leukaemia. Interestingly, it has recently been demonstrated that targeting of chimeric antigen receptors to the endogenous T cell receptor locus using CRISPR-Cas9 improves the efficiency of CAR T cells. The power of this technology is likely to improve and it is likely to be applicable to a broader range of malignancies in the future. Finally it is also likely that engineered haematopoietic cells will be used to treat infectious diseases. It has been shown that allogeneic transplantation with a CXCR5 negative donor can cure HIV. Although trials of engineered lymphocytes with CXCR5 knockdown were unsuccessful for treating HIV, autologous transplantation with HSCs with knockdown of CXCR5 has the potential to be curative analogous to allogeneic transplantation.
The work to be developed in this project is likely to provide a rapid method to identify mutations resulting from genome editing and this has the potential to allow the field to improve the genome editing technology more rapidly. Since developing genome editing technology is an international effort, the research is likely to have a significant impact on the UK profile in this area. If successful the impact of the research could be very rapid indeed (within 12 months).
Publications
Aljahani A
(2022)
Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF.
in Nature communications
Cacciottolo T
(2019)
Scientific Business Abstracts of the 113th Annual Meeting of the Association of Physicians of Great Britain and Ireland
in QJM: An International Journal of Medicine
Crump NT
(2021)
BET inhibition disrupts transcription but retains enhancer-promoter contact.
in Nature communications
Downes DJ
(2021)
High-resolution targeted 3C interrogation of cis-regulatory element organization at genome-wide scale.
in Nature communications
Title | Genome architecture |
Description | Collaboration with Emilis Balustratis who is a concept artist to create an artwork to represent genome architecture. The project aims create images that humanise the scale of the genome and its architecture to allow our work to be accessible to a lay audience. |
Type Of Art | Artwork |
Year Produced | 2021 |
Impact | The artwork was produced to accompany our publication in Nature. We plan to use the work in public engagement exercises such as the Cheltenham Science Festival. |
Description | Bio-modifying Technologies workshop |
Geographic Reach | National |
Policy Influence Type | Membership of a guideline committee |
Impact | Attended the ESRC-funded workshop run by Michael Morrison which had the following aims: 1. How to understand the specific' and distinctive 'experimental space' for gene editing as both a critical tool for basic research and a 'gateway' technology with multiple potential biomedical applications from next generation CAR-T therapies to in vivo gene editing. 2. The challenges this space carries especially in regard to the development of products and prospective clinical delivery 3. Reporting on the results of an MHRA-hosted Patient Forum coordinated by the project 4. The current UK activity in each area and the wider global landscape in each area 5. Lessons from the social sciences and how these can be drawn on in each field |
URL | https://www.regmednet.com/esrc-biomodifying-technologies-policy-briefing-3/ |
Description | Blood and Transplant Research Unit in Precision Cellular Therapeutics |
Amount | £4,000,412 (GBP) |
Funding ID | NIHR203339 |
Organisation | National Institute for Health Research |
Sector | Public |
Country | United Kingdom |
Start | 04/2022 |
End | 04/2027 |
Description | Decoding human non-coding disease genetics en masse using Micro Capture-C and Deep Neural Network Machine learning |
Amount | £3,738,985 (GBP) |
Funding ID | 225220/Z/22/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2022 |
End | 09/2027 |
Description | Lister Research Prize Fellowship |
Amount | £250,000 (GBP) |
Organisation | Lister Institute of Preventive Medicine |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 10/2022 |
End | 10/2027 |
Description | Precise long-term modification of the immune response using genome editing for the treatment of multiple IMIDs with shared pathophysiology |
Amount | £249,580 (GBP) |
Funding ID | MR/T030410/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2021 |
End | 06/2022 |
Title | Micro Capture-C Method |
Description | We have developed a novel chromosome conformation capture methodology, which allows 3D contacts between different sequences within the nucleus to be determined at base pair resolution. This is a very significant advance on previous methods, which are unable to determine contacts much below 500-1000 base pairs. |
Type Of Material | Technology assay or reagent |
Year Produced | 2021 |
Provided To Others? | No |
Impact | The method forms part of the technology used to form a spin out company (Nucleome Therapeutics) and patent application has been filed for the method, which has been licensed to Nucleome Therapeutics. |
Title | Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF |
Description | This data shows contact data from the important genes controlling the fate of embryonic stem cells using a new technique we have developed, which allows the structure of whole genomic loci to be determined at up to 20bp resolution. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | The data are significantly higher resolution than has been previously been possible (around 10 fold better). This has shown that DNA forms much smaller scale structures at gene promoters and enhancer than was previously thought. This has broad implications for understanding how genes are controlled across all eukaryotic life. |
URL | https://www-ncbi-nlm-nih-gov.ezproxy.u-pec.fr/geo/query/acc.cgi?acc=GSE181694 |
Title | Defining genome architecture at base-pair resolution |
Description | Data defining the enhancer landscape at multiple key genes. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | These data show megabase scale DNA structure at base pair resolution. This is an unprecedented resolution and had provided key insights into how genes are controlled in general. |
URL | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE144336 |
Description | Collaboration to develop new methods of finding sites of lentiviral insertion. |
Organisation | University of Oxford |
Department | Nuffield Division of Clinical Laboratory Sciences |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | My research team have been setting up a new method of determining sites of lentiviral insertion using high throughput sequencing. |
Collaborator Contribution | My partners have provided material for analysis, which has been transfected using their vectors. |
Impact | This collaboration has generated promising preliminary data and we working on making the generation and analysis of the data more robust, with an aim to publish the method. |
Start Year | 2018 |
Description | Collaboration with Dr Shengdar Tsai (St Jude) to use his methods for determining off target effects |
Organisation | St Jude Children's Hospital |
Country | United States |
Sector | Hospitals |
PI Contribution | I have set up a collaboration with Dr Shengdar Tsai to use his most recent method for determining off target effects from genome editing experiments (CHANGE-seq) |
Collaborator Contribution | He has provided detailed protocols and will support us to implement the method in our lab. |
Impact | None as yet |
Start Year | 2018 |
Title | EDITING OF HAEMOGLOBIN GENES |
Description | The present invention relates to a process for producing a modified nucleic acid, wherein the nucleic acid comprises a mutant haemoglobin B (HBB) gene encoding a mutant Hb-ß polypeptide. The process comprises using a base editor, preferably with a gRNA, to edit the mutant HBBgene to change a first (mutant) codon in that gene into a second, non-wild-type codon, wherein the Hb-ß polypeptide encoded by that edited HBBgene has a non-wild-type, yet phenotypically-viable, amino acid sequence. The invention also provides a population of isolated haematopoietic stem cells,the stem cells comprising edited HBBgenes. |
IP Reference | WO2020065303 |
Protection | Patent application published |
Year Protection Granted | 2020 |
Licensed | Commercial In Confidence |
Impact | This patent covers a method of curing sickle cell disease and HbE beta thalassaemia with base editing. These conditions affect over 100,000 births each year and they have an enormous economic and social impact (sickle cell disease is estimated to have an economic burden of over $3 billion dollars per year in the US alone). |
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 | EP3365464 |
Protection | Patent granted |
Year Protection Granted | 2018 |
Licensed | Commercial In Confidence |
Impact | This invention has formed the basis of a spin out biotechnology company. |
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 | US2018312910 |
Protection | Patent granted |
Year Protection Granted | 2018 |
Licensed | Yes |
Impact | This patent formed the basis for us to set up a spin out biotechnology company. |
Title | Micro Capture-C analysis tools |
Description | I wrote the software for analysis of Micro Capture-C and conventional Capture-C data. This has been licensed by Oxford University Innovation to Nucleome Therapeutics Ltd. |
Type Of Technology | Software |
Year Produced | 2019 |
Impact | This software was licensed as part of a spin out company I formed with Prof J. Hughes and Dr D. Jeziorska from the University of Oxford. |
URL | http://www.nucleome.com |
Title | Next Generation Capture-C analysis tools |
Description | This software is used to analyse Capture-C data. It has been licensed to the spin out Nucleome Therapeutics. |
Type Of Technology | Software |
Year Produced | 2020 |
Impact | This software forms part of the Intellectual Property behind a spin out co-founded by me. The spin out raised 5.2 million in the seed round from Oxford Sciences Innovation. |
Company Name | NUCLEOME THERAPEUTICS LIMITED |
Description | Nucleome Limited is a spinout from the University of Oxford with patented technology that defines the 3D structure of the genome allowing us to link disease causing genetic variants located in the non-coding DNA to affected genes. This, together with our computational pipelines, powered by machine learning capabilities, and extensive molecular biology and genetic engineering expertise, forms a platform technology for novel therapeutic target discovery and development. |
Year Established | 2019 |
Impact | The company is an early stage startup. It has secured £5.2 million in seed funding from Oxford Sciences Innovation. The company has considerable interest from several large pharmaceutical companies including GSK and MERK. |
Website | http://www.nucleome.com |
Description | Article for The Conversation on Human Genome Editing |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | I wrote an article on genome editing of human embryos for The Conversation. The article has had over 10,000 readers and was one of the most highly commented on pieces from Oxford University in 2019. |
Year(s) Of Engagement Activity | 2019 |
URL | https://theconversation.com/gm-humans-are-possible-but-do-we-really-want-them-121211 |
Description | Articles in National Press including Times and Telegraph |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Article in the Times and Telegraph News papers about research. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.thetimes.co.uk/article/the-date-with-a-neanderthal-that-led-to-a-million-covid-deaths-3h... |
Description | Assissted with articles in The Times and Daily Mail Online on Genome Editing |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | I was interviewed by Rhys Blakely at the Times and assissted him with writing an article about genome editing in Sickle Cell disease including editing the final article. I also provided comment for the Daily Mail Online. |
Year(s) Of Engagement Activity | 2019 |
Description | Cheltenham Science Festival |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | I was the main speaker at an event at the Cheltenham Science Festival. This was reported in the national media and had widespread engagement including a Youtube video, which has had over 600,000 views. |
Year(s) Of Engagement Activity | 2022 |
URL | https://issuu.com/cheltenhamfestivals/docs/csf_2022_brochure_final |
Description | Co-chair - Association of Physicians of Great Britain and Ireland Early Career Workshop - Exploiting opportunities and building career resilience in the time of COVID-19 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | I co-chaired a virtual meeting entitled 'Exploiting opportunities and building career resilience in the time of COVID-19'. This meeting had a panel representing the large funding bodies and was aimed at assisting early career medical professionals to understand how the research landscape has been affected by the COVID-19 pandemic. |
Year(s) Of Engagement Activity | 2020 |
URL | https://aopgbi.org/meetings-events/webinar-series-emerging-issues-in-medicine/exploiting-opportuniti... |
Description | ITV news interview |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Interview for ITV news for publication describing identification of the gene responsible for doubling the risk of severe COVID-19 |
Year(s) Of Engagement Activity | 2021 |
URL | https://twitter.com/GMB/status/1456508119283011592 |
Description | Interactive presentation and discussion with haemoglobinopathy patient support group |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | I gave a presentation and lead a discussion about the latest developments in genome editing for sickle cell disease and thalassaemia. |
Year(s) Of Engagement Activity | 2019 |
Description | Interview for Article in Nature Biotechnology |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Interview for Nature Biotechnology about the platform we have been developing in my spin out company to mind non-coding human genetics to identify new drug targets. |
Year(s) Of Engagement Activity | 2021 |
Description | Interview for the Australian Broadcasting Corporation television news |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Interview with ABC news about our recent publication describing the major genetic cause of COVID19. |
Year(s) Of Engagement Activity | 2021 |
Description | Press conference and media coverage for COVID genetics |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Press conference for paper which identified the causal gene behind the major genetic signal for COVID-19. This resulted in worldwide media coverage from over 285 news outlets in more than 50 different countries. |
Year(s) Of Engagement Activity | 2021 |
URL | https://nature.altmetric.com/details/116235844 |
Description | Public Patient Involvment evening - Oxford Centre for Advance Cellular Therapy |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Presented and was part of the panel at a PPI evening to consult on the development of a new Oxford Centre for Advanced Cellular Therapy |
Year(s) Of Engagement Activity | 2021 |
Description | Radio interview (BBC news) |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Interview for BBC radio news on paper which identified the major gene causative for severe outcome from COVID-19 |
Year(s) Of Engagement Activity | 2021 |
URL | https://www.bbc.co.uk/news/health-59165157 |
Description | Radio interview BBC world service |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Interview with the world service about our publication describing identification of the most important gene linked to severe COVID-19. |
Year(s) Of Engagement Activity | 2021 |
Description | Supporting the Oxford Blood Group Patient Engagement |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | I attended the Oxford Blood Group event, which brought clinicians, researchers and patients together to discuss ethical issues surrounding research. The event was held in a cinema, where the film 'People are Messy' was shown. The showing of the film was followed by a discussion between the clinicians, researchers and patients surrounding the ethics of patient involvement in research. |
Year(s) Of Engagement Activity | 2018 |