Trends in Genetics
Research updateFive years of vector service for gene therapy
Section snippets
The first gene therapy successes
The first success was achieved at the Necker Hospital in Paris, with treatment of four children suffering from X-linked Severe Combined Immune Deficiency (SCID-X). Patients were auto-grafted with hematopoietic stem cells (HSC) transduced with a retrovirus carrying the wild-type γC gene. This restored normal immune function, all clinical symptoms disappeared, and the children are healthy to date [1]. Marina Cavazzana-Calvo (Necker Hospital, Paris, France) envisages performing additional trials
Other approaches to treatment of genetic diseases
Guerrino Meneguzzi (INSERM-CHU, Nice, France) was able to produce laminin-β3 (LB3) in LB3-deficient keratinocytes from junctional epidermolysis bullosa (JEB) patients [2]. The keratinocytes were transduced with the wild-type LB3 gene using retroviral vectors, which transduced almost 100% of cells, confirming the efficiency of this vector system for epidermal stem cells. The feasibility of treating genetic skin diseases by grafting engineered epidermal stem cells on to human patients is
Fetal gene therapy
Charles Coutelle (Imperial College, London, UK) discussed fetal somatic gene therapy as a preventive approach to the management of human genetic diseases, one which could potentially avoid early onset disease manifestation. A large population of actively dividing cells are present during fetal life, and the fetus has increased immune tolerance to transgenic proteins. Thus, this approach could lead to permanent somatic gene supplementation, and facilitate repeated postnatal treatments. The major
The developments in gene transfer technology
Despite the tremendous progress in research and the initial clinical achievements, many problems remain unresolved, due to the absence of vector standardization with validated procedures of production, purification and quality control. Estuardo Aguilar-Cordova (Harvard University, Cambridge, MA, USA) stressed the requirement for reference standard vector preparations with normalization of their physical and functional characteristics (titer, purity, etc.) [7]. These normalized parameters are
Acknowledgements
The GVPN conference was supported by the European Community-High Level Scientific Conference (Brussels, contract no. HPCF-2001-00 078), the Association Française contre les Myopathies (Evry) and by Amaxa, AMT, BioReliance®, BioRobotics, CleanCells®, Henogen, PlamidFactory, Pyrosequencing, Q-BIOgene, Q-ONE Biotech, QIAGEN and TECAN.
References (7)
Gene therapy for human severe combined immunodeficiencies
Immunity
(2001)Improvement of erythropoiesis in beta-thalassemic mice by continuous erythropoietin delivery from muscle
Blood
(2000)Working toward an adenoviral vector testing standard
Mol. Ther.
(2000)