Discovery, Development, and Application of Synthetic Gene Delivery Systems

Abstract

More than 25 years ago, in a Science article, Friedmann and Roblin outlined prospects for human gene therapy (Friedmann and Roblin 1972). This forward—looking review anticipated the development of two alternative gene delivery systems: viral gene therapy vectors and synthetic gene delivery systems using purified gene sequences. Theoretical support for the use of viruses arose from the knowledge that DNA and RNA tumor viruses were capable of introducing heritable changes into the genome of mammalian cells. Friedmann proposed that, if the deleterious features of these viruses could be eliminated, one might safely deliver a desirable gene to correct cellular defects or genetic disorders. As molecular biology techniques matured, the tools to package genes into nonreplicating, recombinant retroviral vectors became available (Mann et al. 1983). These vectors allowed investigators to introduce recombinant genes into living cells and to permanently transduce them with a new genetic phenotype. During the last 15 years substantial progress has been made to produce safe and effective viral vectors, and we have witnessed an exponential growth in preclinical research and clinical development of recombinant viral vectors for gene therapy applications (Fig. 1).