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Correction of uroporphyrinogen decarboxylase deficiency (hepatoerythropoietic porphyria) in Epstein-Barr virus-transformed B-cell lines by retrovirus-mediated gene transfer: fluorescence-based selection of transduced cells.
Blood. 1999 Jul 15; 94(2):465-74.Blood

Abstract

Hepatoerythropoietic porphyria (HEP) is an inherited metabolic disorder characterized by the accumulation of porphyrins resulting from a deficiency in uroporphyrinogen decarboxylase (UROD). This autosomal recessive disorder is severe, starting early in infancy with no specific treatment. Gene therapy would represent a great therapeutic improvement. Because hematopoietic cells are the target for somatic gene therapy in this porphyria, Epstein-Barr virus-transformed B-cell lines from patients with HEP provide a model system for the disease. Thus, retrovirus-mediated expression of UROD was used to restore enzymatic activity in B-cell lines from 3 HEP patients. The potential of gene therapy for the metabolic correction of the disease was demonstrated by a reduction of porphyrin accumulation to the normal level in deficient transduced cells. Mixed culture experiments demonstrated that there is no metabolic cross-correction of deficient cells by normal cells. However, the observation of cellular expansion in vitro and in vivo in immunodeficient mice suggested that genetically corrected cells have a competitive advantage. Finally, to facilitate future human gene therapy trials, we have developed a selection system based on the expression of the therapeutic gene. Genetically corrected cells are easily separated from deficient ones by the absence of fluorescence when illuminated under UV light.

Authors+Show Affiliations

Laboratoire de Pathologie Moléculaire et Thérapie Génique, FR 60 Biologie des Greffes, Université Victor Segalen Bordeaux 2, Bordeaux, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

10397714

Citation

Fontanellas, A, et al. "Correction of Uroporphyrinogen Decarboxylase Deficiency (hepatoerythropoietic Porphyria) in Epstein-Barr Virus-transformed B-cell Lines By Retrovirus-mediated Gene Transfer: Fluorescence-based Selection of Transduced Cells." Blood, vol. 94, no. 2, 1999, pp. 465-74.
Fontanellas A, Mazurier F, Moreau-Gaudry F, et al. Correction of uroporphyrinogen decarboxylase deficiency (hepatoerythropoietic porphyria) in Epstein-Barr virus-transformed B-cell lines by retrovirus-mediated gene transfer: fluorescence-based selection of transduced cells. Blood. 1999;94(2):465-74.
Fontanellas, A., Mazurier, F., Moreau-Gaudry, F., Belloc, F., Ged, C., & de Verneuil, H. (1999). Correction of uroporphyrinogen decarboxylase deficiency (hepatoerythropoietic porphyria) in Epstein-Barr virus-transformed B-cell lines by retrovirus-mediated gene transfer: fluorescence-based selection of transduced cells. Blood, 94(2), 465-74.
Fontanellas A, et al. Correction of Uroporphyrinogen Decarboxylase Deficiency (hepatoerythropoietic Porphyria) in Epstein-Barr Virus-transformed B-cell Lines By Retrovirus-mediated Gene Transfer: Fluorescence-based Selection of Transduced Cells. Blood. 1999 Jul 15;94(2):465-74. PubMed PMID: 10397714.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Correction of uroporphyrinogen decarboxylase deficiency (hepatoerythropoietic porphyria) in Epstein-Barr virus-transformed B-cell lines by retrovirus-mediated gene transfer: fluorescence-based selection of transduced cells. AU - Fontanellas,A, AU - Mazurier,F, AU - Moreau-Gaudry,F, AU - Belloc,F, AU - Ged,C, AU - de Verneuil,H, PY - 1999/7/9/pubmed PY - 1999/7/9/medline PY - 1999/7/9/entrez SP - 465 EP - 74 JF - Blood JO - Blood VL - 94 IS - 2 N2 - Hepatoerythropoietic porphyria (HEP) is an inherited metabolic disorder characterized by the accumulation of porphyrins resulting from a deficiency in uroporphyrinogen decarboxylase (UROD). This autosomal recessive disorder is severe, starting early in infancy with no specific treatment. Gene therapy would represent a great therapeutic improvement. Because hematopoietic cells are the target for somatic gene therapy in this porphyria, Epstein-Barr virus-transformed B-cell lines from patients with HEP provide a model system for the disease. Thus, retrovirus-mediated expression of UROD was used to restore enzymatic activity in B-cell lines from 3 HEP patients. The potential of gene therapy for the metabolic correction of the disease was demonstrated by a reduction of porphyrin accumulation to the normal level in deficient transduced cells. Mixed culture experiments demonstrated that there is no metabolic cross-correction of deficient cells by normal cells. However, the observation of cellular expansion in vitro and in vivo in immunodeficient mice suggested that genetically corrected cells have a competitive advantage. Finally, to facilitate future human gene therapy trials, we have developed a selection system based on the expression of the therapeutic gene. Genetically corrected cells are easily separated from deficient ones by the absence of fluorescence when illuminated under UV light. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/10397714/Correction_of_uroporphyrinogen_decarboxylase_deficiency__hepatoerythropoietic_porphyria__in_Epstein_Barr_virus_transformed_B_cell_lines_by_retrovirus_mediated_gene_transfer:_fluorescence_based_selection_of_transduced_cells_ L2 - https://ashpublications.org/blood/article-lookup/doi/&lo.doi; DB - PRIME DP - Unbound Medicine ER -