The Biotechnology of Gene Therapy

Abstract

The prospect for correcting highly morbid or fatal inherited diseases, or ameliorating cancer and acquired, deadly infectious diseases such as AIDS using gene therapy is very exciting. Numerous recent advances in molecular biology make it possible, not only to identify and locate genes associated with human inherited disorders and cancers, but to potentially correct these disorders with functional genes. These advances include more rapid gene identification, isolation and sequencing techniques, a better understanding of the functions and relationships between genes and their products in vivo, the development and study of human and model organism genomes, elucidation of genetic disease pathology using animal genetic disease models, advanced computer amino acid and nucleotide sequencing software and data bases, and the development and use of novel chemical, physical, and viral vector gene delivery methods. Functional genes are introduced using two approaches, ex vivo and in vivo gene therapy. In ex vivo therapy, autologous cells are removed from the patient, genetically altered by inserting the functional gene, characterized, and then returned to the patient; in in vivo therapy, functional genes are packaged for delivery directly into the patient, where cellular uptake and gene expression occurs. Scores of clinical trials have been federally approved to treat patients with a variety of inherited disorders, cancers, and acquired diseases using these two approaches. Roadblocks to long-lasting gene therapy include understanding more completely the biological functions of somatic cells or organs targeted for gene therapy, targeting appropriate host cells and achieving high gene delivery rates in these cells, regulating and sustaining gene expression through optimal DNA insertion into chromosomes such that other cellular functions are not adversely affected, and the prevention of vector-induced diseases or cancers. Ethical considerations regarding proper use of somatic gene therapy and the potential for germline gene therapy must also be seriously considered. me prospect of permanent correction of highly morbid or fatal maladies using gene therapy could prove to be one of the great advances in public health and could revolutionize the identification and gene-drug treatment of a broad spectrum of inherited and acquired human diseases.