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Journal articles
Stable and functional lymphoid reconstitution in artemis-deficient mice following lentiviral artemis gene transfer into hematopoietic stem cells.
Fatine Benjelloun
1
Alexandrine Garrigue
1
Corinne Demerens-de Chappedelaine
1
Pauline Soulas-Sprauel
1
Michele Malassis-Séris
1
Daniel Stockholm
2
Julia Hauer
1
Johanna Blondeau
2
Julie Rivière
1
Annick Lim
3
Marc Le Lorc'H
4
Serge Romana
4
Nicole Brousse
5
Frederique Pâques
6
Anne Galy
2
Pierre Charneau
7
Alain Fischer
1, 8
Jean-Pierre de Villartay
1, 9
Marina Cavazzana-Calvo
1, 10, *
*
Corresponding author
2
Généthon
Fatine Benjelloun 1
Author
Alexandrine Garrigue 1
Author
Corinne Demerens-de Chappedelaine 1
Author
Pauline Soulas-Sprauel 1
Author
Michele Malassis-Séris 1
Author
Daniel Stockholm 2
Author IdHAL : daniel-stockholm ORCID : https://orcid.org/0000-0002-5069-5256
Julia Hauer 1
Author
Johanna Blondeau 2
Author
Alain Fischer 1, 8
Author
Jean-Pierre de Villartay 1, 9
Author
Marina Cavazzana-Calvo 1, 10
Correspondent author
1
Developpement Normal et Pathologique du Système Immunitaire (Gh Necker - Enfants Malades PARIS V
149, Rue de Sèvres
75015 PARIS - France)
- UPD5 - Université Paris Descartes - Paris 5 : UMR-S 768 (12, rue de l'École de Médecine - 75270 Paris cedex 06 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : UMR-S 768 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR-S 768 (France)
3
Développement des Lymphocytes (25-28 rue du Docteur Roux F-75724 Paris Cedex 15 - France)
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U668 (101, rue de Tolbiac, 75013 Paris - France)
4
Service d'Histologie-Embryologie et Cytogénétique Assistance Publique (Hôpital Necker-Enfants Malades, Paris - France)
5
Service d'Anatomie et Cytologie Pathologique (Paris - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- UPD5 - Université Paris Descartes - Paris 5 (12, rue de l'École de Médecine - 75270 Paris cedex 06 - France)
- CHU Necker - Enfants Malades [AP-HP] (149 Rue de Sèvres 75015 Paris - France)
7
Virologie moléculaire et Vectorologie (25-28 rue du Docteur Roux 75724 Paris Cedex 15 - France)
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
- CNRS - Centre National de la Recherche Scientifique : URA3015 (France)
8
Unité d'Immunologie et Hématologie Pédiatrique (Hôpital Necker-Enfants Malades, Paris - France)
9
Service d'Hématologie (Hôpital Necker-Enfants Malades, Paris - France)
10
Département de Biothérapie [CHU Necker] (Groupe Hospitalier Necker-Enfants Malades
Localisation du service : Carré Necker porte N5, 1er étage
149 rue de Sèvres 75743 Paris Cedex 15 - France)
- CHU Necker - Enfants Malades [AP-HP] (149 Rue de Sèvres 75015 Paris - France)
- UPD5 - Université Paris Descartes - Paris 5 (12, rue de l'École de Médecine - 75270 Paris cedex 06 - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
Abstract : Patients with mutations in the Artemis gene display a complete absence of T- and B lymphocytes, together with increased cellular radiosensitivity; this leads to a radiosensitive severe combined immunodeficiency (RS-SCID). Allogenic hematopoietic stem-cell (HSC) transplantation is only partially successful in the absence of an human leukocyte antigen-genoidentical donor, and this has prompted a search for alternative therapeutic approaches such as gene therapy. In this study, a self-inactivated lentiviral vector expressing Artemis was used to complement the Artemis knockout mouse (Art(-/-)). Transplantation of Artemis-transduced HSCs into irradiated Art(-/-) mice restored a stable (over a 15-month period of follow-up) and functional T- and cell repertoire that was comparable to that of control mice. The success of secondary transplantations demonstrated that the HSCs had been transduced. One of thirteen mice developed a thymoma 6 months after gene therapy. Although thymic cells were seen to be carrying two lentiviral integration sites, there was no evidence of lentivirus-driven oncogene activation. The Art(-/-) mice were found to be prone to develop T-cell lymphomas, either spontaneously or after irradiation. These data indicate that the observed lymphoproliferation was probably the consequence of the chromosomal instability associated with the Artemis-deficient background. As a whole, our work provides a basis for supporting the gene therapy approach in Artemis-deficient SCID.
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Journal articles
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00457775
Contributor : Mireille Gau <>
Submitted on : Thursday, February 18, 2010 - 2:24:41 PM
Last modification on : Wednesday, August 19, 2020 - 11:16:55 AM
Contributor : Mireille Gau <>
Submitted on : Thursday, February 18, 2010 - 2:24:41 PM
Last modification on : Wednesday, August 19, 2020 - 11:16:55 AM
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Identifiers
- HAL Id : pasteur-00457775, version 1
- DOI : 10.1038/mt.2008.118
- PUBMED : 18560421
Collections
UNIV-PARIS5 | PASTEUR | CNRS | USPC | UNIV-PARIS
Citation
Fatine Benjelloun, Alexandrine Garrigue, Corinne Demerens-de Chappedelaine, Pauline Soulas-Sprauel, Michele Malassis-Séris, et al.. Stable and functional lymphoid reconstitution in artemis-deficient mice following lentiviral artemis gene transfer into hematopoietic stem cells.. Molecular Therapy, Nature Publishing Group, 2008, 16 (8), pp.1490-9. ⟨10.1038/mt.2008.118⟩. ⟨pasteur-00457775⟩
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