Len Seymour - Overview

Research in this laboratory is focused on translational application of gene therapy for the treatment of cancer. We provide scientific, pharmacokinetic and pharmacodynamic support for ongoing clinical trials using adenovirus vectors injected directly into tumours, and simultaneously are developing better vectors capable of targeted and efficient delivery of therapeutic transgenes to target tumour cells in vivo. On one level this work involves development of "stealth" adenoviruses, capable of avoiding neutralisation by antibodies. These vectors can be retargeted to infect target cells via specific internalising receptors, and we are developing long circulating forms suitable for systemic targeting of disseminated tumour cells. Such systems can be very versatile, and could be used for delivery of both viruses encoding suicide enzymes, and also for conditionally replicating viruses that will selectively destroy cancer tissue following delivery through the barrier of neutralising antibodies. The other approach we are developing is based on completely synthetic vectors, formed by self assembly of plasmid DNA with polycations, avoiding any safety issues associated with the use of viruses. Such synthetic vectors can also be designed for targeted delivery to tumour cells in vivo, and can contain functionalities capable of promoting endosomal escape, passage through the nuclear membrane and episomal maintenance. When fully developed these non-viral vectors will be easier to produce in bulk and should be more acceptable in clinical use than vectors based on viruses. In a variation on this theme we are studying the useful properties of specific viral proteins to identify those that can be usefully incorporated into synthetic vectors. By promoting a multidisciplinary research team, involving virologists, chemists and cell and molecular biologists, we aim to combine the best aspects of viral and non viral delivery systems, to develop effective gene therapies for cancer.