Advances in gene therapy in humans: Basic concepts and a historical journey

Gene therapy has promised to revolutionize medicine since the concept of treating disease by using viruses to replace damaged DNA in a patient with corrected DNA was introduced in the 1970s. The first working model was tested in mice, in the 1980s. In the 1990s, gene therapy strategies began to be used to treat some immune and nutritional deficiencies, with limited success. Later, in 1999, a patient died in a gene therapy trial due to complications associated with a severe immune response against the gene vector. This tragedy temporarily brought the entire field to a halt. Research recovered slowly but steadily, until 2012, when the discovery of CRISPR, a technology that enables easy and precise modifications of human genes, strongly reinvigorated the entire field. This review presents the fundamentals of gene therapy and a historical journey with the main milestones that occurred in the last 50 years.