Targeting a Pre-existing Anti-transgene T Cell Response for Effective Gene Therapy of MPS-I in the Mouse Model of the Disease.


Journal

Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581

Informations de publication

Date de publication:
03 07 2019
Historique:
received: 01 02 2019
revised: 12 04 2019
accepted: 14 04 2019
pubmed: 8 5 2019
medline: 27 2 2020
entrez: 8 5 2019
Statut: ppublish

Résumé

Mucopolysaccharidosis type I (MPS-I) is a severe genetic disease caused by a deficiency of the alpha-L-iduronidase (IDUA) enzyme. Ex vivo hematopoietic stem cell (HSC) gene therapy is a promising therapeutic approach for MPS-I, as demonstrated by preclinical studies performed in naive MPS-I mice. However, after enzyme replacement therapy (ERT), several MPS-I patients develop anti-IDUA immunity that may jeopardize ex vivo gene therapy efficacy. Here we treat MPS-I mice with an artificial immunization protocol to mimic the ERT effect in patients, and we demonstrate that IDUA-corrected HSC engraftment is impaired in pre-immunized animals by IDUA-specific CD8

Identifiants

pubmed: 31060789
pii: S1525-0016(19)30180-7
doi: 10.1016/j.ymthe.2019.04.014
pmc: PMC6612662
pii:
doi:

Substances chimiques

Antibodies, Monoclonal 0
Immunoglobulin G 0
Iduronidase EC 3.2.1.76

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1215-1227

Informations de copyright

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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Auteurs

Giorgia Squeri (G)

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; International PhD Program in Molecular Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy.

Laura Passerini (L)

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.

Francesca Ferro (F)

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA 02115, USA; Program for Gene Therapy in Rare Diseases, Department of Medicine, Boston Children's Hospital, Boston, MA 02115, USA.

Cecilia Laudisa (C)

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.

Daniela Tomasoni (D)

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.

Federica Deodato (F)

Division of Metabolic Disease, Bambino Gesù Children's Hospital IRCSS, 00165 Rome, Italy.

Maria Alice Donati (MA)

Metabolic and Neuromuscular Unit, Meyer Children Hospital-University of Florence, 50139 Florence, Italy.

Serena Gasperini (S)

Pediatric Department, Fondazione MBBM San Gerardo Hospital, 20900 Monza, Italy.

Alessandro Aiuti (A)

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Vita-Salute San Raffaele University, 20132 Milan, Italy.

Maria Ester Bernardo (ME)

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.

Bernhard Gentner (B)

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.

Luigi Naldini (L)

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Vita-Salute San Raffaele University, 20132 Milan, Italy.

Andrea Annoni (A)

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.

Alessandra Biffi (A)

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA 02115, USA; Program for Gene Therapy in Rare Diseases, Department of Medicine, Boston Children's Hospital, Boston, MA 02115, USA.

Silvia Gregori (S)

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. Electronic address: gregori.silvia@hsr.it.

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Classifications MeSH