This project looks to develop a platform technology that utilises external stimuli, such as light for the triggered polymer un-coating of viral vectors for in-vivo targeted delivery. We will use the Truetype AAV serotype vector, with strong neurotropism to deliver to the brain. We will utilise NIR light to cause un-coating of polymer coated viral vectors. By coating viral vectors with polymers via a photo-responsive linkage it will be possible to target the un-coating in-vivo using light. In this way, polymer coating can allow for a decrease in immune responses, accumulation and lead to increased circulation times, whilst being easily removed at the target site for controlled delivery of the viral vector. This could revolutionise the way in which we treat damaged tissue in-vivo by, for example, allowing for targeted modifications that lead to regeneration of damaged cardiac tissue, neurons, or muscle cells in-situ.
Applications of gene therapies have become commonplace. Typically viral vectors are used ex-vivo for this genetic modification, on account of their excellent nuclear transfer efficiencies, broad tissue tropism and low pathogenicity. Viral vectors have struggled to find use in in-vivo applications as they have been shown to illicit an immune response and are typically sequestered in the liver. Polymer coating can be used to overcome both of these problems whilst also improving circulation times. However, polymer coating completely inhibits the ability of the viral vectors to infect. If it existed, a simple method to remove this polymer coat at the intended in-vivo site would significantly improve in-vivo gene therapies. For example, it would be possible to repair damaged neurons, cardiac tissue or muscles in-situ. This project looks to develop a platform technology that utilises light-cleavable linkages between viral vectors and polymers to allow for NIR light-triggered un-coating of the polymer shell. Once developed, this platform technology can then be utilised with a wide range of viral vectors for the repair of a wide range of cells, tissues and/or organs.
Due to the multidisciplinary nature of this project, students from a variety of backgrounds are welcomed. The successful candidate will have experience with polymer synthesis and characterisation and/or experience of working with viral vectors. Specifically experience of functionalization of viral capsids/envelopes will be advantageous but not critical. You will be a trustworthy, conscientious, independent experimental scientist who is able to work as part of a larger team.
At the University of Manchester, we pride ourselves on our commitment to fairness, inclusion and respect in everything we do. We welcome applications from people of all backgrounds and identities, and encourage you to bring your whole self to work and study. We will ensure that your application is given full consideration without regard to your race, religion, gender, gender identity or expression, sexual orientation, nationality, disability, age, marital or pregnancy status, or socioeconomic background. All PhD places will be awarded on the basis of merit.
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