Marina Cavazzana-Calvo *[1,2,3], Salima Hacein-Bey *[1,2,3], GeneviŠve de Saint Basile
. Fabian Gross , Eric Yvon , Patrick Nusbaum , Fran‡oise Selz , Christophe Hue
[1,2], St‚phanie Certain , Jean-Laurent Casanova [1,4], Philippe Bousso , Fran‡oise Le
Deist , Alain Fischer [1,2,4], "Gene Therapy of Human Severe Combined Immunodeficiency
(SCID)-X1 Disease," Vol. 288, No. 5466, pp. 669-672, Science (April 28, 2000).
Severe combined immunodeficiency-X1 (SCID-X1) is an X-linked inherited disorder
characterized by an early block in T and natural killer (NK) lymphocyte differentiation. This block
is caused by mutations of the gene encoding the c cytokine receptor subunit of interleukin-2, -4,
-7, -9, and -15 receptors, which participates in the delivery of growth, survival, and differentiation
signals to early lymphoid progenitors. After preclinical studies, a gene therapy trial for SCID-X1
was initiated, based on the use of complementary DNA containing a defective c Moloney
retrovirus-derived vector and ex vivo infection of CD34+ cells. After a 10-month follow-up
period, c transgene-expressing T and NK cells were detected in two patients. T, B, and NK cell
counts and function, including antigen-specific responses, were comparable to those of
age-matched controls. Thus, gene therapy was able to provide full correction of disease
phenotype and, hence, clinical benefit.
1. INSERM Unit 429,
2. Gene Therapy Laboratory,
3. Cell Therapy Laboratory,
4. Unite d'Immunologie et d'Hematologie Pediatriques, Hopital Necker, 75743 Paris Cedex 15, FRANCE.
5. INSERM Unit 277, Institut Pasteur, 75730 Paris, FRANCE.
* These authors contributed equally to this work.
To whom correspondence should be addressed at INSERM Unit 429, Hopital Necker-Enfants Malades, 149 rue de Sevres, 75743 Paris Cedex 15, FRANCE;. E-mail: email@example.com .
For a related article in Science:
W. French Anderson, "The Best of Times, the Worst of Times," Vol. 288, No. 5466, pp. 627- 629, Science (April 28, 2000)(in Perspectives).