Prospects and problems of gene therapy: an update

Abstract

The gene therapy approach can vary from delivering extra copies of a gene, through modifications of a genome using the properties of ribozymes or chimeraplasts, to injection of modified cells. For the treatment of genetic deficits the ultimate goal would be the repair of the mutated gene in the target tissue(s). The techniques required for such an approach are emerging, albeit slowly. Therefore, delivery of an extra copy of a normal gene in a specific vector remains the predominant approach. Moreover, this method finds wider applications in gene therapy relating to disorders other than heritable defects, e.g., malignancies, cardiovascular diseases and infections. The major and most intensive areas of research are: i) vectors and delivery methods, ii) regulation of transgene expression and iii) stability of expression. Targeting of the therapeutic gene is being accomplished by using viral vectors or non-viral delivery systems, either ex vivo or in vivo. The choice of vectors and delivery routes depends on the nature of the target cells and the required levels and stability of expression. Although there have been the first positive clinical results and significant technical achievements over the past 2 years, there are still obstacles to the development of effective clinical products and these remain largely unchanged. The most important barriers are the low levels and stability of expression and immune responses to vectors and/or gene products. The safety aspects of gene therapy have become painfully evident with the first death conclusively linked to gene therapy. The progress in AAV and lentiviral vectors, improved regulation of transgene expression and advances in stem cell technology are among the recent most exciting developments.

• AAV
• adenovirus
• artificial chromosome
• gene therapy
• herpesvirus
• immunogenicity
• lentivirus
• plasmid
• retrovirus
• stem cell
• vector