Genome medicine: gene therapy for the millennium.

Abstract

The Genome Medicine: Gene Therapy for the Millennium meeting provided a forum for discussion of scientific advances stimulated by the explosion of sequence information generated by the Human Genome Project. Genome medicine can be seen as a discipline whose focus is on genetic information that defines both the genetic basis of the disease and therapeutic modalities for optimal treatment of disease pathology. Not only does this information facilitate the functional evaluation of genes via biochemical analysis and through animal models, it is also the basis for development of novel therapeutic strategies. Developments in the modification of cells by genetic intervention have led to gene therapy as a therapeutic modality. The goal of gene therapy is to correct genetic defects by gene transfer. Despite the technical difficulties associated with the transfer of therapeutic DNA, the number of gene therapy trials in humans is increasing. Most of these trials are based on viral gene transfer (e.g., adenovirus, adeno associated virus and retrovirus). The use of virus-based approaches may be limited by insertional mutagenesis and host immune responses that attenuate gene therapy efficacy [1]. While it appears that there has been some clinical success with retroviral gene therapy, other viral systems have proven more recalcitrant. Recent studies involving nonviral transfer implantation of genetically altered fibroblasts that produce Factor VIII into patients with severe haemophilia A have been encouraging [2]. The ultimate goal of gene therapy for inherited diseases is for specific and controllable studies aimed at direct rectification of mutated genes in hereditable disorders. In this respect, homologous replacement, gene repair and artificial chromosomes have particular appeal. Combined with the development of new DNA transfer vehicles and stem cell technology, there is potential for effective implementation of these therapies [3-5].