The development of gene therapy

Haema 2016; 7(1): 45-56

by Evangelia Yiannaki1,2, Varnavas Constantinou1, George Stamatoyannopoulos2

1Gene and Cell Therapy Center, Haematology Department and Bone Marrow Transplantation Unit, “G. Papanikolaou” Hospital, Thessaloniki, Greece,
2Department of Medicine and Markey Molecular Medicine Center, University of Washington, Seattle, WA, USA

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Abstract

The aetiologic treatment of diseases at the genetic level is called gene therapy and it has been a theoretical objective of medicine since the ’70s, when genetic diseases were directly associated to gene mutations. In the ’80s, the first experimental approaches for gene therapy had to address two basic issues: the development of tools (vectors) to transfer the therapeutic genetic material into the cells and the type of cells to be targeted. In the early ’90s, following the tremendous progress of biotechnology, gene therapy moved to the level of clinical trials, albeit without the expected success. This lack of efficacy indicated the need of return back to basic research and rational design of clinical protocols. The first great success of gene therapy came in 2000, when children suffering from X-SCID, a lethal immunodeficiency, were cured with the use of a gamma retroviral vector for the transfer of the therapeutic gene to the hematopoietic stem cells. This indisputable success of gene therapy, however, was overshadowed by the recognition of treatment-associated toxicity in the form of insertional oncogenesis, which necessitated the development of new and safer vectors or even new methods for the genetic modification. Today, hundreds of clinical trials are conducted worldwide for difficult to cure, both hereditary and acquired diseases, using safer and more efficient viral vectors (lentiviral, AAV vectors) and producing remarkable results in many cases. Moreover, the field of gene therapy is constantly expanding; gene editing, a method which offers targeted and theoretically safer genetic modification opening the door to a range of novel theurapeutic approaches, is expected to be the next advancement of gene therapy. This review presents a historical overview of gene therapy, with emphasis on important and seminal points of its development and evolution.