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Advances in the gene therapy of monogenic blood cell diseases
Author(s) -
Bueren Juan A.,
QuintanaBustamante Oscar,
Almarza Elena,
Navarro Susana,
Río Paula,
Segovia José C.,
Guenechea Guillermo
Publication year - 2020
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13593
Subject(s) - genetic enhancement , haematopoiesis , genome editing , hematopoietic stem cell , medicine , viral vector , gene , stem cell , thalassemia , adverse effect , gene delivery , sickle cell anemia , hematopoietic stem cell transplantation , bioinformatics , biology , computational biology , immunology , cell , genome , genetics , recombinant dna
Hematopoietic gene therapy has markedly progressed during the last 15 years both in terms of safety and efficacy. While a number of serious adverse events (SAE) were initially generated as a consequence of genotoxic insertions of gamma‐retroviral vectors in the cell genome, no SAEs and excellent outcomes have been reported in patients infused with autologous hematopoietic stem cells (HSCs) transduced with self‐inactivated lentiviral and gammaretroviral vectors. Advances in the field of HSC gene therapy have extended the number of monogenic diseases that can be treated with these approaches. Nowadays, evidence of clinical efficacy has been shown not only in primary immunodeficiencies, but also in other hematopoietic diseases, including beta‐thalassemia and sickle cell anemia. In addition to the rapid progression of non‐targeted gene therapies in the clinic, new approaches based on gene editing have been developed thanks to the discovery of designed nucleases and improved non‐integrative vectors, which have markedly increased the efficacy and specificity of gene targeting to levels compatible with its clinical application. Based on advances achieved in the field of gene therapy, it can be envisaged that these therapies will soon be part of the therapeutic approaches used to treat life‐threatening diseases of the hematopoietic system.