Current Gene Therapy - Volume 14, Issue 6, 2014

The Wiskott-Aldrich Syndrome (WAS) is a monogenic X-linked primary immunodeficiency characterised also by thrombocytopenia, eczema, and a high susceptibility to develop tumours and autoimmunity. WAS patients have a severely reduced life expectancy, unless they undergo a successful HLA-matched haematopoietic stem cell (HSC) transplantation. However, several WAS patients lack a compatible donor and complication Read More

Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome is a rare autoimmune disease due to mutations in the gene encoding for Forkhead box P3 (FOXP3), a transcription factor fundamental for the function of thymus-derived (t) regulatory T (Treg) cells. The dysfunction of Treg cells results in the development of devastating autoimmune manifestations affecting multiple organs, eventually lea Read More

Over the last few years, the transfer of therapeutic genes via gammaretro- or lentiviral vector systems has proven its virtue as an alternative treatment for a series of genetic disorders. The number of approved phase I/II clinical trials, especially for rare diseases, is steadily increasing, but the overall hurdles to become a broadly acceptable therapy remain numerous. The efforts by clinicians and basic scientists have tremen Read More

Haemophagocytic lymphohistiocytosis (HLH) describes a severe and often fatal immunodysregulatory disorder caused primarily by the uncontrolled activation and proliferation of T cells and macrophages. A number of genetic defects mainly involving defective granule exocytosis and effector cell cytotoxicity have been identified and well characterised at the molecular and cellular level. These conditions have limited therapeutic op Read More

Several Phase I/II clinical trials aiming at the correction of X-linked CGD by gene transfer into hematopoietic stem cells (HSCs) have demonstrated the therapeutic potential of gene modified autologous HSCs for the treatment of CGD. Resolution of therapy-resistant bacterial and fungal infections in liver, lung and spinal canal of CGD patients were clearly documented in all trials. However, clinical benefits were not sustain Read More

Generation and precise genetic correction of patient-derived hiPSCs have great potential in regenerative medicine. Such targeted genetic manipulations can now be achieved using gene-editing nucleases. Here, we report generation of cystic fibrosis (CF) and Gaucher’s disease (GD) hiPSCs respectively from CF (homozygous for CFTRΔF508 mutation) and Type II GD [homozygous for β-glucocerebrosidase (GBA) 1448T Read More

Epigenetics means gene expression alterations which occur due to the biochemical changes of the nucleotides modifying structure of DNA rather than the changes in the genetic code itself as in case of mutations. The epigenome, consisting of chromatin and its modifications, acts as a link between the inherited genome and the changes imposed by the environment. Over the past decade, there has been mounting evidence Read More