Gene Therapy for Human Disease

A major objective of gene therapy research and current treatments is to correct mutations that are responsible for disease. An improved understanding of DNA cell and molecular biology has led to the use of genetic engineering strategies and gene repair mechanisms. The chapter starts with engineering of T cells for CAR-T cell treatment of acute lymphoblastic leukemia. Isolated T cells are genetically modified to produce chimeric antigen receptors (CARs) for the treatment of leukemia. A gene addition strategy to overcome gene mutations is considered for two diseases. These are inherited blindness due to mutation of the RETINAL PIGMENT EPITHELIUM65 (RPE65) gene and hemophilia B due to deficiency or dysfunction of the Factor IX protein. Gene-editing approaches have been applied to a number of disease states. Homology-directed repair (HDR) and base editing to correct sickle cell disease are discussed. In addition to gene editing, epigenetic modification without sequence change, using a modified CRISPR-Cas, is another approach to modify gene expression. The final part of the chapter deals with the treatment of mitochondrial disease by mitochondrial replacement treatment (MRT) and a novel mitochondrial base-editing system. This latter topic raises the question of germline therapy.