Viruses as therapeutic agents: science fiction becomes reality

The idea of using genes as medicines was initially proposed in 1972 by Friedmann and Roblin before it was possible to identify specific genes within genomes, before the discovery of restriction enzymes to cut and paste DNA, and before the development of efficient gene delivery vehicles such as viral vectors [1]. The idea of using genes as medicines to treat diseases was a logical outcome of the identification of complex diseases resulting from mutations in single genes. If complex phenotypes were the result of mutations in a single gene, gene replacement into the right tissue at the right developmental stage should suffice to prevent or even reverse the disease progression. The implementation of this originally simple idea has ushered in a new and exciting era of therapeutic molecular medicine (i.e., gene therapy). Over the past 15 years, hundreds of gene therapy clinical trials have been implemented demonstrating therapeutic results in a growing number of genetic disorders, from relatively simple monogenic inborn errors of metabolism to complex diseases such as cancer.

The techniques required to implement gene transfer began to appear in the early 1980s with the development of viral vectors (i.e., disabled viruses that could function as gene delivery vehicles). Mouse leukemia retroviruses were among the first viral vector systems that were converted into effective gene transfer vectors. By replacement of viral genes with a potentially therapeutic gene the virus was rendered incapable of replication and thus, producing disease.