Please use this identifier to cite or link to this item:
Scopus Web of ScienceĀ® Altmetric
Type: Journal article
Title: Long-term in vitro correction of alpha-L-iduronidase deficiency (Hurler syndrome) in human bone marrow
Author: Fairbairn, L.
Lashford, L.
Spooncer, E.
McDermott, R.
Lebens, G.
Arrand, J.
Arrand, J.
Bellantuono, I.
Holt, R.
Hatton, C.
Cooper, A.
Besley, G.
Wraith, J.
Anson, D.
Hopwood, J.
Dexter, T.
Citation: Proceedings of the National Academy of Sciences of USA, 1996; 93(5):2025-2030
Issue Date: 1996
ISSN: 0027-8424
Statement of
L. J. Fairbairn, L. S. Lashford, E. Spooncer, R. H. McDermott, G. Lebens, J. E. Arrand, J. R. Arrand, I. Bellantuono, R. Holt, C. E. Hatton, A. Cooper, G. T. N. Besley, J. E. Wraith, D. S. Anson, J. J. Hopwood, and T. M. Dexter
Abstract: Allogeneic bone marrow transplantation is the most effective treatment for Hurler syndrome but, since this therapy is not available to all patients, we have considered an alternative approach based on transfer and expression of the normal gene in autologous bone marrow. A retroviral vector carrying the full-length cDNA for alpha-L-iduronidase has been constructed and used to transduce bone marrow from patients with this disorder. Various gene-transfer protocols have been assessed including the effect of intensive schedules of exposure of bone marrow to viral supernatant and the influence of growth factors. With these protocols, we have demonstrated successful gene transfer into primitive CD34+ cells and subsequent enzyme expression in their maturing progeny. Also, by using long-term bone marrow cultures, we have demonstrated high levels of enzyme expression sustained for several months. The efficiency of gene transfer has been assessed by PCR analysis of hemopoietic colonies as 25-56%. No advantage has been demonstrated for the addition of growth factors or intensive viral exposure schedules. The enzyme is secreted into the medium and functional localization has been demonstrated by reversal of the phenotypic effects of lysosomal storage in macrophages. This work suggests that retroviral gene transfer into human bone marrow may offer the prospect for gene therapy of Hurler syndrome in young patients without a matched sibling donor.
Keywords: Hematopoietic Stem Cells
Cells, Cultured
Bone Marrow
Mucopolysaccharidosis I
DNA Primers
Antigens, CD34
Gene Expression
Base Sequence
Genetic Vectors
Time Factors
Molecular Sequence Data
Genetic Therapy
DOI: 10.1073/pnas.93.5.2025
Published version:
Appears in Collections:Aurora harvest
Environment Institute Leaders publications
Paediatrics publications

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.