INTRODUCTION

It is fair to say that almost all diseases, whether acquired or inherited, have at their foundation a genetic aetiology. The understanding of the molecular basis of disease and the recent acquisition of ‘genetic’ tools have made it feasible to consider the notion of repairing damaged genes (e.g. inherited diseases) or removing rogue genetic elements (e.g. cancers, viruses and bacteria) as a viable therapeutic objective. But what is gene therapy? Although definitions may vary, in essence gene therapy refers to any procedure intended to treat or alleviate disease by genetically modifying the cells of a patient. Often, although not always, gene therapy involves the artificial introduction of genetic material (such as DNA or RNA) into cells. Since DNA and RNA are relatively large nucleic acid macromolecules, their successful introduction rests on developing delivery systems that are capable of carrying macro - molecules to diseased cells.

At present gene therapy remains an experimental technique with tremendous promise for the future of medicine. In this chapter different types of gene-based therapeutic approaches are outlined, with the focus being on innovative experimental technologies that are most likely to obtain clinical success. The topic of gene delivery will be discussed by comparing the strengths and weaknesses of viral and non-viral delivery systems

SOMATIC VS GERMLINE GENE THERAPY

Germline gene therapy. This form of gene therapy requires the introduction of genetic material (DNA or RNA) into sperm or oocytes to produce permanent, transmissible modification. Germline gene therapy is considered to be unethical and in some countries is illegal. In addition, this type of intervention may not necessarily solve the problem. For example, for many recessive disorders, carriers maintain the frequency of the dominant allele.

Somatic gene therapy. All current gene therapy treatment modalities aim to introduce genetic material into somatic cells, although, unlike germline therapy, such an approach is unlikely to produce permanent modifications of the targeted cells. Long-term trans mission of genes can be achieved by utilising viral vectors capable of integrating into quiescent (non-dividing) cells or by targeting stem cells.