2000 IRISH SCIENTIST YEAR BOOK

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Virus vectors for gene therapy and new virus vaccines

The Health Research Board & Trinity College Dublin
Greg Atkins

Electron micrograph of a Semliki Forest virus infected cell showing virus particles and intermediate stages in viral replication.

Research on virus diseases in recent times has focused on molecular determinants of viral function and host defence against infection. In the past few years, it has become apparent that some characteristics of viruses, which normally contribute to disease, may be manipulated to treat disease rather than cause it. Thus viruses are being developed as vectors for vaccine construction, as gene therapy agents, and as cancer therapy agents.

A vector is a manipulated virus which can be used to express non-viral therapeutic genes for the treatment or prevention of disease. The first virus vectors to be developed were based on DNA viruses, such as adeno or adeno-associated virus, or RNA viruses which synthesis a stable DNA copy of their genome - such as retroviruses. We are developing a new virus vector system based on the Semliki Forest virus (SFV) genome. This is an RNA virus which comes from Africa and, although it infects man, it is normally asymptomatic. The advantage of using an RNA virus is that it has enhanced biosafety because it persists in tissue for only short lengths of time, but it also shows very high levels of expression compared to other vectors. It can thus be used as a substitute for drugs because it expresses therapeutic genes in treated tissue and is then eliminated.

We are using SFV as a vector to construct new recombinant vaccines which may have several advantages over current vaccines and can be manipulated to increase biosafety and to stimulate the correct type of immune response. We are also developing this vector as a prototype treatment for neurological disease such as multiple sclerosis, to carry therapeutic genes into the nervous system. As a cancer therapy agent, we are developing the vector to induce programmed cell death or apoptosis in tumour cells, and to target tumour tissue.

This work is collaborative and multi-disciplinary, and is carried out in collaboration with Professor Brian Sheahan at the Veterinary College, UCD, and Professor Peter Liljestr_at the Karolinska Institute, Stockholm. It is supported by the Health Reasearch Board, the Wellcome Trust, the EU, the Multiple Sclerosis Society, the Irish Cancer Society, and BioResearch Ireland.



Contact: Professor Greg Atkins,
Virus Group,
Moyne Institute of Preventive Medicine, Trinity College Dublin;
E-mail: gatkins@tcd.ie ;
Web: http://www2.tcd.ie/Microbiology/ page225.html