In vivo delivery of gene therapy to tumours

A problem presented at the UK MMSG Oxford 2005.

Presented by:
Dr Kerry Fisher (Clinical Pharmacology, University of Oxford)
Dr Len Seymour (Clinical Pharmacology, University of Oxford)
L Band, R Booth, L Cummings, R Dyson, K Fisher, I Griffiths, J Moles, L Seymour, S Waters

Problem Description

Virus particles are often used to deliver gene therapy to tumours in the body. They are injected into the blood stream and enter tumours through gaps in the lining of the capillaries. Little is understood about the effect of the gap size, flow rate and the size of both the particles and the capillary itself on how many particles are able to reach the tumour. The MMSG investigation will look at how the particles are distributed within the blood flow and will examine the mechanisms for how the particles leave the blood stream. We will draw on the expertise used for a related problem at the first MMSG.

Download the full problem description

Study Group Report

In this report we focused on three different aspects of the biological problem. First we studied the macroscale problem of flow through an entire tumour. We modelled the tumour as a porous medium and we assumed the virus particles are point particles which are passively advected by the blood flow.

Secondly, we studied the flow into a single gap between endothelial cells. Assuming the virus particles are small compared with the size of the gap and are passively advected with the blood flow, we found virus particles within an entrainment region would enter the tumour. However if the gap size is comparable to the virus particle size, the presence of the virus particle influences the blood flow.

Finally we studied the encapsulated virus particle. Stresses from the blood flow will deform the virus's membrane. Thus the physical properties of the virus particle influence its motion close to the wall and this motion may significantly affect the number of virus particles which enter the tumour.

Download the full report