1996
DOI: 10.1159/000203880
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Simulation of Hematopoiesis: Implications for the Gene Therapy of Lysosomal Enzyme Disorders

Abstract: Although the hematopoietic stem cell is an attractive target for gene transfer, little is known about its biology in vivo in large animals (including humans). We have studied the in vivo behavior of hematopoietic stem cells in glucose-6-phosphate dehydrogenase heterozygous (female Safari) cats, and demonstrated that clonal instability persists for up to 4.5 years after autologous marrow transplantation. This contrasts with the 2-6 months of clonal disequilibrium reported in comparable murine studies. Our data … Show more

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Cited by 7 publications
(4 citation statements)
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“…The level of gene transfer seen in these studies, while suboptimal, is predicted to have potential therapeutic impact in hematopoietic cell-based gene therapy for iduronidase deficiency (Neufeld, 1991;Scott et al, 1995;Abkowitz et al, 1996). The retroviral vectors used in this study carried the normal canine iduronidase cDNA and/or the neo r gene and provided good levels of gene transfer into hematopoietic progenitors and stem cells in other canine gene transfer studies by our group (Bienzle et al, 1994;Shull et al, 1996a;.…”
Section: Discussionmentioning
confidence: 99%
“…The level of gene transfer seen in these studies, while suboptimal, is predicted to have potential therapeutic impact in hematopoietic cell-based gene therapy for iduronidase deficiency (Neufeld, 1991;Scott et al, 1995;Abkowitz et al, 1996). The retroviral vectors used in this study carried the normal canine iduronidase cDNA and/or the neo r gene and provided good levels of gene transfer into hematopoietic progenitors and stem cells in other canine gene transfer studies by our group (Bienzle et al, 1994;Shull et al, 1996a;.…”
Section: Discussionmentioning
confidence: 99%
“…Gene therapy has great potential for treating LSDs, due to possible long-term transduction of affected cells, and the bystander effect of secreted lysosomal enzymes, including NaGlu. 25 27 The adeno-associated viral (AAV) vector system has been widely studied as a gene delivery tool for treating various diseases, with demonstrated therapeutic effect. The recombinant AAV (rAAV) vectors have a broad spectrum of tissue tropism, which can be varied through the use of different serotypes.…”
Section: Introductionmentioning
confidence: 99%
“…8 Moreover, NaGlu shares many properties with other lysosomal enzymes, which can be secreted and taken up by neighboring cells and transported to the lysosomes, resulting in broader distribution via a bystander effect. [9][10][11] Generally speaking, for MPS disorders, only 1-2% residual enzyme activity may be needed to normalize cell function. Therefore, it would not be necessary to transduce all cells for effective MPS IIIB treatment.…”
Section: Introductionmentioning
confidence: 99%