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Directed Evolution of Targeting Strategies for Precise Delivery of Genome Editors to Hematopoietic Stem Cells Using Extracellular Vesicles and Lipid Nanoparticles

This project is part of the Therapeutic Genomics Centre, a multidisciplinary programme of innovative approaches to treating rare genetic disorders and providing an enhanced training experience for DPhil applicants.

Academic Supervisors: Prof. Matthew P.A Wood, Assoc. Prof. James Davies

Other Supervisors: Dr. Dhanu Gupta

Host Dept: Paediatrics, Oxford

Our central hypothesis is that engineered extracellular vesicles (EVs) can serve as innovative and non-immunogenic delivery mechanisms for in vivo genome editing of hematopoietic stem cells (HSCs). By leveraging CRISPR-Cas9 technology within these delivery systems, we aim to target and correct gene mutations that underlie genetic blood-based disorders. A crucial aspect of this project involves performing directed evolution of EV targeting domains using a library of nanobodies. This approach will enable us to achieve precise ex vivo and in vivo HSC targeting, providing a significant advantage over currently available non-specific HSC targeting strategies.

These engineered nanobodies will not only enhance the specificity and efficiency of EV-based delivery but will also be adapted to synthetic delivery platforms such as lipid nanoparticles (LNPs), broadening the scope and applicability of our genome editing strategy. By integrating these advanced targeting mechanisms, we anticipate significantly improving the precision and safety of gene editing therapies for genetic blood disorders. This project aligns with the Therapeutic Genomics Centre’s mission to advance translational research by bridging the gap between basic research and clinical application, ultimately offering potential pathways for improving patient outcomes and revolutionizing the treatment landscape for genetic blood disorders.

Studentship code: MRCTGCORE2024007

Please read these guidance notes for detail on how to apply

Click here to apply: IPP login screen (ox.ac.uk)

For more information on DPhil in Paediatrics: DPhil in Paediatrics | University of Oxford

For more information about our MRC-Oxford Doctoral Training Programme see: https://www.medsci.ox.ac.uk/study/graduateschool/mrcdtp