Razi Journal of Medical Sciences

Human gene therapy has attracted increasing attention as a highly encouraging therapeutic approach to treat wide variety of diseases, other than genetically inherited and monogenic disorders. This approach entails the introduction and expression of a variety of nucleic acids into human target cells for therapeutic purposes. In this article, we review the history, highlights, recently progresses and future of gene therapy approaches.

The first gene therapy clinical trial was successfully performed in 1990s for treating an inherited genetic disorder, Severe Combined Immunodeficiency (SCID). Subsequently, the number of gene therapy clinical trials was exponentially continued to increase over the years. However, the initial results of these trials did not meet expectations.

In the last decade, due to improvements in the gene transfer vectors, the dreams of treating severe immunodeficiency and genetic disorders and cancer by gene therapy products is again closer to reality. Before gene therapy becomes an extensively accepted approach for treating wide range of diseases, some limitative intracellular and extracellular barriers need to be overcome. Currently, a wide range of gene delivery vectors have been developed to do this. A number of safe viral vectors and non-viral methods were innovated and used for successfully treatment of some inherited and immune deficiencies, ocular diseases and cancer. Viral gene delivery vectors are appropriate for gene therapy purposes which are based on long-term gene expression. Although, non-viral vectors are less efficient than former in gene transduction, they have utilities owing to their high target cell specificity, low immunogenicity and ability to transfer large size genes.

In conclusion, recent progress in the gene therapy approaches is somewhat realizing expectancies made many years ago, providing bright hopefulness for further achievements in the next years. Gene therapy appears to be final selective approach for the treatment of many human diseases in this century.