Jose Carlos Segovia

Gene Therapy for Inherited Anemias: From Lentiviral to Gene Editing Strategies

Cell Technology Division. Biomedical Innovation Unit. CIEMAT, Madrid

Dr. Jose-Carlos Segovia is Doctor in Biological Sciences by the Universidad Autónoma de Madrid. Currently, he is Head of the Cell Technology Division and of the Flow Cytometry and Cell Separation Laboratory (LACISEP), at the Center for Energy, Environmental and Technological Research (CIEMAT). He has published more than 100 scientific articles in high-impact journals in the areas of Gene and Cell Therapy, has participated in more than 45 projects, being Principal Investigator of more than 12. He has filed 10 patents, one4 of them already licensed to biotechnology companies (Rocket Pharmaceuticals [New York]; DanausGT Biotechnology [Madrid, Shanghai, Wuxi]). He has developed gene therapy protocols for the treatment of inherited anemias (Pyruvate Kinase Deficiency [PKD], Congenital Dyserythropoietic Anemia type II [CDAII]). He has achieved orphan drug designation by the European Agency and the American Drug Agency (EMA and FDA, respectively) for addition lentiviral based and CRISPR/Cas9 edition gene therapy drugs, already being tested in a first-in-human clinical trial. Lastly, he has been secretary of the Spanish Society of Gene and Cell Therapy and he is currently vice-president of the Iberian Society of Cytometry.



“Gene Therapy for Inherited Anemias: From Lentiviral to Gene Editing Strategies”

Advanced gene and cell therapy for the treatment of genetic diseases is a growing field that will allow the treatment of inherited diseases with unmet needs. Thanks to the development of lentiviral based gene addition strategies, an important number of genetic diseases affecting the hematopoietic system have been addressed. Up to now, 4 indications have been already approved for commercialization in Europe and/or in USA. Recently, the discovery of the CRISPR/Cas9 bacterial protection system against bacteriophages and their adaptation to allow the precise editing of genomes has allowed the generation of very precise sequence specific genetic modifications. Gene editing in the presence of therapeutic DNA template has opened the possibility of site-specific gene therapy, avoiding potential risks of insertional oncogenesis. Here, we show that the application of these strategies to hemolytic anemias, such us Pyruvate Kinase Deficiency, is allowing the cure of the disease in patients by means of a lentiviral vector strategy (Clinical trial NCT04105166). Four patients have already been treated with a longer follow up of three years, with an almost complete cure of the disease. Moreover, the application of gene editing technologies will further improve the precision of the therapy in the future. In this regard, we have developed a clinically applicable strategy for the site-specific gene therapy of this disease. Overall, gene addition and gene editing approaches allow the development of gene therapies as the definitive cure for those devastating rare diseases with unmet treatment.