Viral Vectors for Gene Therapy of Genetic Diseases: Challenges and Prospects

Abstract

Viruses naturally possess specialized molecular mechanisms to efficiently transfer their genetic materials into the infected cells. Viral vectors can be used to modify specific cell type or tissue and can be directed to express therapeutic genes. These unique abilities made them desirable for engineering viral vectors to deliver the therapeutic genes. The efficient delivery of therapeutic genes and correct gene expression are important for clinically relevant gene therapy. The most commonly used viral vectors are derived from retroviruses, adenoviruses, and adeno associated viruses (AAV). Gene therapy has a turbulent history because of failure of the first clinical trial. Jesse Gelsinger [1] who was suffering from a partial deficiency of ornithine trans carbamyalse (OTC), took part in a gene therapy clinical trial at the University of Pennsylvania, Philadelphia. Due to immune responses caused by a high dose of adenoviral vector containing OTC, Gelsinger died four days later because of multi-organ failure [1]. In another clinical trial conducted in France and UK, among twenty X-linked severe combined immunodeficiency disease (X-SCID) patients, 19 were successfully cured their immunodeficiency by retroviral vector containing IL-2RG (γc). Four of the treated patients developed T cell leukemia because the gamma retrovirus integrated in/near the proto-oncogenes that turned the gene on. But the patients were successfully treated with chemotherapy and in complete remission [2].