Gene therapy of severe combined immunodeficiencies

Recent advances in gene transfer in human hematopoietic cells, combined wit h a better understanding of the genetic aspects of several immunodeficienci es, has offered new opportunities in the domain of gene therapy. Severe com bined immunodeficiency (SCID) appear to represent a good model for the appl ication of gene therapy, combining an expected selective advantage for tran sduced cells, an absence of immunological response to the vector and/or the therapeutic transgene, together with accessibility to hematopoietic stem c ells (HSC). Ex vivo retroviral transduction of a therapeutic transgene in H SC prior to transplantation appears to be a particularly effective and long -lasting means of restoring the expression of a mutated gene in the lymphoi d lineage. Furthermore, encouraging therapeutic benefits as a result of a g ene therapy protocol for the treatment of X-linked severe combined immunode ficiencies (SCID-X1) invites many questions as to the reasons for this ther apeutic benefit. This review outlines the results that have been achieved i n gene therapy for SCID-X1, ADA-SCID as well as other types of SCID, and di scusses the possible relationship between the physiopathology of each disea se and the success of relevant trials. Copyright (C) 2001 John Wiley & Sons , Ltd.