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  BBSRC PhD Studentship in Repurposing an endogenous human mRNA transfer system as a gene therapy tool


   Department of Biochemical Engineering

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  Dr D Nesbeth, Prof Dan Bracewell  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

About the Project

This project aims to map out the feasibility and performance of a naturally-ocurring system for mRNA transfer in humans when repurposed to deliver recombinant RNA payloads. The system involves a single protein that, upon translation, associates with its encoding mRNA then forms a particle that sequesters that mRNA, after which the particle is enveloped within vesicles that bud into a multivesicular body (MVB) before cellular release and virus-like transfer to target cells in which the payload mRNA is released for subsequent translation.

Gene therapy approaches have recently faced challenges due in part to adverse effects arising from the immunogenicity of the viral vectors used for tgene transfer. Kumin et al. (2021) report that, on average, 35% of 149 2021 AAV gene therapy clinical trials were associated with treatment-emergent serious adverse events.

In this project the Protein X mRNA will be modified to test its capacity to incorporate recombinant RNA elements. Inserted elements of differing size and sequence will be tested for their ability to be transferred from packaging cells to target cells via the engineerred Protein X system. It is anticipated that the immunogenicity of a Protein-X system will be significantly lower than that of virus-based systems.

 

About the BBSRC Collaborative Training Partnership in Advanced Bioscience of Viral Products (ABViP)

This PhD studentship is part of the Biotechnology and Biological Sciences Research Council (BBSRC) Collaborative Training Partnership (CTP) in Advanced Bioscience of Viral Products (ABViP). The ABViP CTP is a comprehensive, multidisciplinary training programme designed to deliver the next generation of bioscience leaders who will advance research on the underpinning bioscience of viral products for future gene therapies and vaccines. Led by Oxford Biomedica (OXB) and involving both UCL and the University of Oxford, CTP students will have access to a wide-ranging portfolio of training opportunities at the Partner sites including taught courses and case studies designed to complement the doctoral research. Students trained through the ABViP CTP will gain a holistic insight into the research and development activities required to develop the medicines of the future, with the ability to see the world of medicines development through both an academic and industrial lens. For more information about the ABViP CTP, please click on the following link.

About the Department

This project is based in the Department of Biochemical Engineering at UCL, a world leader in bioprocess research creating novel engineering solutions to underpin future biomanufacturing processes. The Department of Biochemical Engineering represents one of the major bioprocessing groups in the world, where high-impact research activity is undertaken with a strong industry focus, linking advanced bioscience to an understanding of whole bioprocesses by which discoveries are translated into healthcare outcomes. The Department has superb facilities for biochemical engineering research with significant impact on the bioprocessing and biomanufacturing of cell and gene therapies, biologics, vaccines, oligonucleotides, regenerative medicines, high-value chemicals, pharmaceuticals and biomaterials. Researchers in our Department make use of the recent >£30m of investment in comprehensive and unique facilities including a fully equipped pilot-plant.

Additional information about research in the Biochemical Engineering department can be found at https://www.ucl.ac.uk/biochemical-engineering/.

About Oxford Biomedica

Oxford Biomedica (OXB) is a pioneer of gene and cell therapy with a leading position in viral vector research and bioprocessing. Our mission is to deliver life-changing gene therapies to patients. OXB is an innovation and science focussed company which has developed a leading platform of novel technologies and capabilities. The OXB team provide design, development, bioprocessing and analytical development for gene-based medicines based on viral vectors, both for in-house products and for those developed with partner organisations. OXB has contract development and manufacturing organisation (CDMO) capabilities that support the development of novel gene-based medicines through all phases of clinical development to commercial manufacture. At Oxford Biomedica, we drive credible science to realise incredible results.

Entry requirements

A UK Master’s degree, or a minimum of an upper second-class UK Bachelor’s degree, in a relevant discipline, or an overseas qualification of an equivalent standard. We particularly welcome applicants from disadvantaged backgrounds, or via an unconventional career path. If you’re unclear as to whether you are eligible, we would encourage you to apply regardless. You can also contact the project supervisor (see details below). To learn more about the policies in relation to diversity and inclusion at UCL, please click here for further information.

Informal enquiries should be addressed to Darren Nesbeth (E-mail [Email Address Removed]).

Funding

This BBSRC CTP ABViP Studentship is available to UK and Overseas (including EU) students. Full maintenance (stipend & fees) is available to the UK and Overseas students for the duration of the four-year PhD. Note that up to a maximum of one fully funded studentship allocation is available for Overseas students across the Department. The annual tax-free stipend for the PhD studentship is £20,198 (estimated value, confirmed annually, using in spring by UKRI and UCL).

English language requirements

If your education has not been conducted in the English language, you will be expected to demonstrate evidence of an adequate level of English proficiency. The English language level for this programme is: Level 1

Deadline and Application Process

The deadline for submission is 12:00 midday on Friday 16th December 2022

To apply for this PhD studentship, you must submit a formal application to the Research Degree: Biochemical Engineering RRDBENSING01 course through UCL’s application portal by the above deadline. More information about the course and application process is available here: https://www.ucl.ac.uk/prospective-students/graduate/research-degrees/biochemical-engineering-mphil-phd


Biological Sciences (4)

Funding Notes

This BBSRC CTP ABViP Studentship is available to UK and Overseas (including EU) students. Full maintenance (stipend & fees) is available to the UK and Overseas students for the duration of the four-year PhD. Note that up to a maximum of one fully funded studentship allocation is available for Overseas students across the Department. The annual tax-free stipend for the PhD studentship is £20,198 (estimated value, confirmed annually, using in spring by UKRI and UCL).