rologie i - European Congress of Virology

5 th European Congress of VirologyGene therapy has become an attractive alternative therapeutic strategy toallogenic hematopoietic stem cell transplantation for primary immunodeficiencies.Clinical trials using gammaretroviral vectors have demonstrated the proofof principle for SCID-X1, Adenosine deaminase, Wiskott-Aldrich syndromeand chronic granulomatous disease, but have also highlightedlimitations of the technology. New strategies based on self-inactivated vectorsthat can achieve more robust corrections with less risk of insertionalmutagenesis are being developed.Methods for integration site recovery that allow for efficient monitoringof integration site abundance while minimizing methodologicalbiases have been set up. Clustering of integration sites was thus comparedbetween these different vectors showing a significant lowerintegration frequency near “dangerous genes” when SIN vectors areused.Despite this improvement hematopoietic, gene therapy approach presentsspecific issues as the use of patients’ bone marrow stem and precursorcells which may have an abnormal composition with unpredictableconsequences. Thus the long-term clinical results of on-going trials usingself-inactivated vectors are eagerly awaited with the expectation that theywill better define the role of gene therapy with respect to conventionalHSCT.S38 Virologie, Vol 17, supplément 2, septembre 2013