Development of an analytical platform for the purification and characterisation of AAV viral vectors for applications in gene therapies

We invite applications for a 3.5 year EPSRC-funded PhD studentship to work under the supervision of Prof Mark Dickman, Prof David James and Prof Mimoun Azzouz in the Neuroscience Institute at the University of Sheffield.
Gene therapy applications have emerged as a powerful new approach in the biopharmaceutical industry. Gene therapies promise versatile treatment options with potential to revolutionise and transform medicine. Such therapies offer the possibility of long-term and potentially curative benefits to patients with genetic or acquired diseases. Gene therapies are designed to treat disease by delivering genetic material that encodes a protein with a therapeutic effect into a patient’s cells. It can be used to replace a missing or faulty gene or correct the effects of a mutant gene, for example, with gene editing. Genetic material can be delivered to a patient’s cells either in vivo or ex vivo.
Although a number of molecular vectors and techniques are available for delivering therapeutic genetic material to target cells, it is most frequently achieved by using viruses that can be administered in vivo to patients either locally or systemically. Several types of viruses can be used as delivery vehicles to infect and transfer a functional gene into patient’s cells. However, vectors centred on the non-pathogenic adeno-associated virus (AAV) have emerged as the vector of choice for many therapies.

In contrast to biotherapeutics such as proteins and nucleic acids, viruses such as AAV are much larger in size and complexity, making them challenging to purify and characterise. It also is crucial that an efficient downstream purification process maintains the biological activity of an AAV vector while removing impurities and contaminants.
The overall aim of this studentship is to develop an analytical platform for the purification and characterisation of AAV based vectors used as gene therapies to treat disease. The proposed research will involve the biomanufacturing of AAV based vectors and the development of novel methods to purify and characterise AAV based vectors.