Lentiviral Mediated Correction of Genetic Disorders

Abstract

Recently lentiviral vectors (LVs) have emerged as potent and versatile vectors for gene transfer into cells. Use of LVs has now moved beyond the preclinical stage into the clinical arena with multiple gene therapy trials ongoing or approved for the treatment of genetic/ metabolic disorders. LVs can deliver genes ex vivo into bona fide stem cells, particularly hematopoietic stem cells, allowing for stable transgene expression upon hematopoietic reconstitution. In the last decade, gene therapy has established itself as a promising approach for the treatment of hereditary diseases of the blood-forming system, especially for patients who cannot be treated by conventional transplantation strategies. However, despite these advances, for many envisioned applications of lentivirus vectors as tools in biology and therapeutic gene delivery in the future, the efficiency of gene transfer still needs to be further studied and improved. Additionally, there are safety concerns regarding insertional mutagenesis. The focus of this review is to highlight some important investigations in which lentiviral vector technology platform was employed to provide a robust ammunition in the quest to develop improved therapeutics to treat otherwise incurable genetic diseases like glycogen storage disease type Ia, β- thalassemias and X linked severe combined immunodeficiency syndrome.