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Development of a manufacturing process for pilot scale synthesis of MIP nanoparticles for therapeutic studies and plasmapheresis

  • Full or part time
  • Application Deadline
    Tuesday, March 12, 2019
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

The studentship aims at development of a manufacturing process for pilot scale synthesis of nano-sized molecularly imprinted polymers (nanoMIPs) for therapeutic studies. The main task of the project will be to develop a synthesis of nanoMIPs via anti-idiotype imprinting. Whole virus capsids will be used as templates in producing first generation of nanoMIPs that mimic anti-AAV antibodies. These nanoMIPs will serve as templates in producing second generation of nanoMIPs acting as binders for anti-AAV antibodies. NanoMIPs will be used in producing large quantity of synthetic binders for anti-AAV antibodies. Synthesis of nanoparticles will be made using the automatic solid-phase photoreactor developed by partner ULEIC. Characterisation of the binding between MIPs and antibodies will be made using surface plasmon resonance. Further characterisation will be made using DLS and TEM. Particular attention will be paid to the selection and development of synthetic approaches compatible with large scale manufacturing and leading to the production of nanoparticles with controlled size distribution, physical and chemical properties.

A prototype of a plasmapheresis column based on anti-AAV-specific nanoMIPs bound to a clinically approved plasmapheresis matrix platform will be generated. Efficiency and specificity of depletion of anti-AAV antibodies will be assessed in vitro and in vivo. Binding capacity of prototype column for anti-AAV antibodies and resin specificity will be tested on real samples such as human plasma specimens obtained from commercial sources and IV Ig. The column developed using MIP technology will be carefully compared to commercially available columns for immune absorption focusing on efficiency and specificity of binding of anti-AAV antibodies.

CureCN

The overall vision of the European research project CureCN is to provide a curative gene therapy for the ultra-rare Crigler-Najjar syndrome (CN). CN is a life-threatening, so far incurable liver disease that affects about one in a million individuals at birth. Caused by the deficiency of a liver-specific substance (uridine diphosphate Glucuronosyltransferase 1A1), toxic unconjugated bilirubin is accumulated in serum and body tissue leading to irreversible neurological damage in the brain. Currently, there is no curing treatment available apart from liver transplantation. Treatment with phototherapy reduces the symptoms, but is very debilitating and loses its efficacy over time. The CureCN consortium joins forces to prove the safety and efficacy of the gene therapy in a clinical trial and to make the treatment available to patients.

How to Apply

Please use the following link: https://www2.le.ac.uk/research-degrees/phd/applyphd

Apply for Chemistry Research.
In the funding section of the application please indicate European Union’s Horizon 2020
Include the supervisor’s name and project title in the Proposal section.

Funding Notes

3 year fully funded studentship as part of the project “Developing a curative gene therapy for Crigler-Najjar syndrome” (CureCN) supported by European Union’s Horizon 2020 research and innovation programme.

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