Empty virus-like particles (eVLPs) as bio-compatible targeted drug-delivery vehicles

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A major challenge in pharmacology is to devise methods whereby drugs can be delivered specifically to target tissues. This is a particular issue in the case of anti-cancer drugs. They usually discriminate between cancerous and normal cells by the fact that the cancer cells are dividing more rapidly; however they are actually toxic to all cells and thus often have severe side-effects. To avoid this, it would clearly be desirable to target the drug molecule specifically to the cancerous tissue. A potential means of achieving this would be to encapsulate the drug molecules inside a particle which is designed to bind solely to the cancerous tissue. Such encapsulation would have the additional advantage of protecting the drug from breakdown in blood plasma. For this to become a reality it will be necessary to develop particles which can be modified on their outer surface to achieve the desired targeting and which can encapsulate drug molecules. This project addresses the above challenge by exploiting the recent discovery at the John Innes Centre of a method of producing large quantities of pure empty (RNA-free) virus-like particles (eVLPs) of CPMV in plants. The method involves simultaneously expressing genes coding for a precursor of the viral coat proteins and the enzyme used to process it using a recently developed highly efficient plant transient expression system. Using this approach we will produce particles which are modified so that they will specifically bind to proteins expressed on the surface of cancerous, but not normal, cells. This modification will be done either chemically or by making genetic fusions to the virus coat protein. We will investigate the best way of loading the targeted particles with the anti-cancer drugs. The ability of the targeted particles to deliver the drug to cancer cells will be investigated by testing their ability to bind to and kill cancers in culture.

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