According to historical landmark events, the development of gene therapy can be roughly divided into four stages: initial exploration, fanatic development, stumbling and advancing, and prosperity again.
In 1963, the American molecular biologist, Nobel Prize winner in Physiology or Medicine, Joshua Lederberg first proposed the concept of gene exchange and gene optimization, which laid the foundation for the development of gene therapy; in 1970, American doctor Stanfield Rogers tried to treat a pair of sisters with arginine by injecting a papillomavirus containing arginase, which was the first human trial that ended in failure. In the following decades, scientists have carried out a number of clinical trials, but the treatment technology is still immature during this period, so the development of gene therapy has always been ignorant.
In 1990, Dr. William French Anderson, who was later called "the father of gene therapy", led a gene therapy for severe combined immunodeficiency disease. The patient was a 4-year-old American girl. After receiving treatment, the body's ability to produce adenosine deaminase was improved, and the girl’s condition was relieved, and the patient is still alive. Two years later, another clinical trial of gene therapy was successful. Since then, the enthusiasm of patients, doctors, and scientists has been quickly ignited, and the industry has entered a period of frenetic development, with thousands of clinical trials conducted over the past 10 years. Overall, gene therapy in this period has achieved initial success, but there are still significant security risks in the technology, and the industry has entered a short period of irrational development.
Stumbling and advancing
In 1999, American boy Jesse Gelsinger participated in the gene therapy program at the University of Pennsylvania. After 4 days of treatment, he died of multiple organ failure due to a strong immune response caused by the virus. This event is a turning point in the development of gene therapy. In addition, the FDA temporarily suspended all clinical trials using retrovirus to engineer blood stem cell genes in 2003, but after a three-month rigorous review of trade-offs, gene therapy clinical trials were allowed to continue. The gene therapy in this period has developed in technology compared with the 1990s, but there are still major security risks, and the industry as a whole develops rationally.
In 2012, Glybera of UniQure in the Netherlands was approved for marketing in the European Union for the treatment of severe muscle diseases caused by lipoprotein lipase deficiency. In the same year, Jennifer Doudna and Chinese-American scientist Zhang Feng invented the CRISPR/CAS9 gene editing technology, a revolutionary event in the field of gene therapy. Since then, some bottlenecks in gene therapy technology have been broken, and both effectiveness and safety have improved, and the industry has ushered in a new round of development climax.
The application of genetic editing is becoming broader and the potential is widening. It is a major development direction in the future. Previously, due to the limitation of the first generation of gene editing technology, ZFN patent monopoly, the development of the entire gene editing industry has been stagnant for many years. With the emergence of a new generation of gene editing technologies (TALEN and CRISPR), the development speed of the industry is expected to increase significantly, and gene therapy will reach a new level.