Gene Therapy and Viral Vectors

Abstract

Gene therapy is the administration of a normal gene to replace a defective gene and thus cure or alleviate suffering from genetic diseases. Researchers are currently looking at a number of genetic diseases as targets, such as severe combined immunodeficiency (SCID), cystic fibrosis, and hemophilia, among others. In most cases, the genes are incorporated into a viral vector. These viruses may have a segment of genetic material removed and replaced with a “normal” gene, known as a “transgene.” The first clinical trial, which was a failure, was in 1980, when a small number of patients with thalassemia were treated with the human globin DNA. In 1995 the first successful trial was performed in children with a defect in adenosine deaminase (ADA) (SCID-syndrome). Treatment of SICD-X1 children, a condition leading to immunodeficiency, was also successful, but the retrovirus vector underwent integration into the host chromosome, resulting in a few cases of leukemia and one death. A large number of different viral vectors have been designed for use in gene therapy, including retrovirus, lentivirus, adenovirus and parvovirus. These are each discussed separately. Despite great efforts and a large number of clinical trials, only one vector system—AAV, Glybera—has been approved for gene therapy for the treatment of patients with lipoprotein lipase deficiency, a rare genetic disease.