Gene Therapy Innovation and Manufacturing Centre (GTIMC)

Lead Research Organisation: University of Sheffield
Department Name: Neurosciences


Gene therapies rely on engineered virus carriers as vehicles for the delivery of synthetic genes that allow correction of disease-altered changes in multiple organs of the human body. Viruses exploited in gene therapy approaches have been modified to remove harmful properties and carry the therapeutic gene of interest. Multiple gene therapy programmes are currently undertaken in research laboratories using relatively small-scale production of viruses which enables optimisation of the doses and administration routes as well as testing for the safety and therapeutic efficacy of interventions in animal models of disease. However, facilities required for the production of large quantities of clinical-grade viruses of consistent quality-controlled GMP grade are rare in the UK. Thus, it can easily take several years before clinical trials can be conducted. Currently, existing facilities cannot meet the escalating demand of academically-led research needs for clinical-grade virus carriers. This is significantly obstructing numerous UK-funded world-leading disease-modifying discoveries to be translated into clinical trials for human benefit. The lack of suitable GMP facilities seriously hinders the development of much-needed novel effective treatments for multiple incurable diseases which cannot be treated by conventional drug compounds. We propose to address the manufacturing shortage by creating a Gene Therapy Innovation and Manufacturing Centre (GTIMC) which includes provision of a new state-of-the-art GMP manufacturing facility to support gene therapy projects emerging from UK universities. GTIMC will also support the development of improved viral vectors, improved yield from the manufacturing process and will also provide essential regulatory and training support. Moreover, the GTIMC hub will allow new training and high-skilled employment opportunities through the ShefVec facility itself, and future start-up companies.

Technical Summary

Current UK facilities for manufacturing viral vectors suitable for human treatment cannot meet demand, thus seriously hindering the translation stage of moving exciting gene therapies into clinical trials. Our aim is to establish a Gene Therapy Innovation and Manufacturing Centre (GTIMC) to address key challenges facing academic groups. The GTIMC will integrate multidisciplinary partners from the Midlands, Wales and North of England with the aim to bring complementary expertise that we have identified as essential components to unravel the existing knowledge gaps focused on adeno-associated virus (AAV) manufacturing, analytics, process innovation, safety, regulatory, clinical pathways, training and commercialisation. The GTIMC includes provision of a new build state-of-the-art GMP manufacturing facility (ShefVec). This new facility, alongside the existing excellent track record and exciting initiatives in gene therapy research within the hub, will cement the hub as a leader in innovation, manufacturing and human gene therapy translational research. ShefVec, to be GMP accredited, will utilise highly efficient purification processes to generate clinical grade AAV and provide all the necessary quality assurance, regulatory certification and governance. ShefVec will enable provision of clinical grade material for human trials at Advanced Therapies Treatment Centres, the NHS hospitals Trusts within the GTIMC and the National Network. Merit, which was a key supplier for the Catapult build in Stevenage, proposes ShefVec to be constructed using a modular design. GTIMC will also develop a translational team, including a solid regulatory platform, to support further development and commercialisation of the selected projects. The hub offers opportunities for expanding training and skills through existing MSc courses in advanced therapies, ATTC training, links to the apprenticeship community, and establishing new PhD programmes in this space.
Description Gene Replacement for Spastic Paraplegia type 47: Clinical Grade Manufacturing
Amount £881,178 (GBP)
Organisation LifeArc 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2023 
End 04/2026
Description Gene Therapy Innovation and Manufacturing Centre
Amount £500,000 (GBP)
Organisation University of Sheffield 
Sector Academic/University
Country United Kingdom
Start 12/2021 
End 07/2022
Description The University of Sheffield application for LifeArc Pathfinder Award
Amount £500,000 (GBP)
Organisation LifeArc 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2023 
End 02/2025
Description Gene Therapy Innovation and Manufacturing Centre (GTIMC) 
Organisation Cell and Gene Therapy Catapult
Country United Kingdom 
Sector Private 
PI Contribution Project funded by the MRC and LifeArc to establish a Gene Therapy Innovation & Manufacturing Centre (GTIMC) in Sheffield. Several partners across the North of England, Midlands and Wales are participating in this initiative. Lead: Mimoun Azzouz
Collaborator Contribution Cell & Gene Therapy Catapult: - Tech transfer AAV platform. - Assay standardisation. - Training through ATAC. - Regulatory engagement University of Sheffield: - GTIMC management - GMP manufacturing. - Gene therapies delivery to patients - Process innovation - Training and skills - Regulatory engagement MW- ATTC: - Clinical pathways for gene therapy delivery - Training Genomic Laboratory Hub: - Access to clinicians, patients and research groups in rare disease - Networking links to other Genomic Laboratory Hubs Lonza AG - Downstream manufacturing AAV platforms for commercialisation - Training and placements Birmingham Women's and Children's Hospital - Gene therapy trials in haematological, metabolic, and neuromuscular disorders Leeds Teaching Hospitals - Delivery of AAV therapies to patients with rare diseases - Training and skills University of Liverpool: - AAV safety and immunogenicity - Genomic Laboratory Hub North-West: Rare diseases NIBSC: - Reference materials - Standardising analytical methods - Training in regulatory sciences. Universities of Bradford & York: - Rare diseases - Training and skills University of Leicester - Data sciences - EU rare diseases network CPI: - Process development and scale-up for AAV. - Scalable manufacturing solutions transfer to ShefVec. Cobra Biologics: - GMP grade plasmid and vector for late phase and commercialisation. - Training: manufacturing, analytics, regulatory affairs. ATAC: - Upskill apprentices. - Use GTIMC MSc Course to develop Levels 6/7 apprenticeship programmes. Northern Health Science Alliance - Source partners through NHSA member organisations. - Secure investment into the Hubs. LifeArc Translational Support: - Regulatory engagement - IP and commercialisation
Impact The award will start in July 2021
Start Year 2021
Description Rare Conversations Conference 2022: Rare Disease Policies: Pioneering the way towards a resilient ecosystem 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact This high-level conference will wrap up the overarching theme of Rare Conversations 2022, "Powering the next decade of rare disease innovation in Europe", by bringing together the input from previous episodes (also at national level) and the expertise of a broad range of representatives of the rare disease community, to build recommendations on the way forward for the rare disease ecosystem, especially in preparation of the upcoming revision of the EU Regulation on orphan medicinal products (OMP Regulation).
The event will, therefore, reflect on several aspects that may be included in the new legislative framework, trying to answer the question: "How to build a resilient rare disease ecosystem for the next decade?".
The conference will also present Alexion's 30-year anniversary campaign, under the motto "Pioneering Complement Science Then and Now". Alexion will share its efforts to empower the future rare disease ecosystem with the goal to continue delivering transformative therapies for people living with a rare disease.
During the overarching opening session, the European Expert Group on Orphan Drug Incentives will present its work and proposals on how to build a sustainable rare disease ecosystem, in connection to the revision of the OMP Regulation. Then, the panels will focus on specific aspects to analyse, by listening to the voices of experts in the field. A breakout session will be dedicated to partnerships for the future, and how a partnership approach can address key outstanding challenges. The conference will conclude with a discussion on the possible policies to adopt to favour innovation and set access, with a particular attention to the regulatory approach to reach these goals.
The final goal will be to make clarity on existing opportunities, and try to identify shared solutions from different stakeholders, to pioneer the rare disease ecosystem. National experts will be involved to give voice to peculiarities that need to be taken into account in specific Member States. The discussion will also be held at a political level, by inviting EU policymakers that will lead the works in the EU Institutions.
Year(s) Of Engagement Activity 2022
Description Visit by Chi Onwurah, the shadow minister for science, research and innovation to GTIMC 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Policymakers/politicians
Results and Impact It was an opportunity to engage with politicians to highlight:
- GTIMC as an example of how University of Sheffield can convene different funding streams (public, private, philanthropy, university), including UKRI MRC, to develop centres of excellence that support new innovation.
- To stress the importance of EU funding for our research activities: highlighting impacts of some prestigious award won by PI (Azzouz) e.g. ERC Advanced and ERC PoC Awards, IMI and JPND. Have discussed the importance of association with Horizon
Year(s) Of Engagement Activity 2022