Restoration of normal lysosomal function in mucopolysaccharidosis type VII cells by retroviral vector-mediated gene transfer

John H. Wolfe, Edward H. Schuchman, Lawrence E. Stramm, Elizabeth A. Concaugh, Mark E. Haskins, Gustavo D. Aguirre, Donald F. Patterson, Robert J. Desnick, Eli Gilboa

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Retroviral vectors were constructed containing a rat β-glucuronidase cDNA driven by heterologous promoters. Vector-mediated gene transfer into human and canine β-glucuronidase-deficient mucopolysaccharidosis type VII fibroblasts completely corrected the deficiency in β-glucuronidase enzymatic activity. In primary cultures of canine mucopolysaccharidosis type VII retinal pigment epithelial cells, which contain large amounts of undegraded glycosaminoglycan substrates, vector correction restored normal processing of specific glycosaminoglycans in the lysosomal compartment. In canine mucopolysaccharidosis type VII bone marrow cells, β-glucuronidase was expressed at high levels in transduced cells. Thus, the vector-encoded β-glucuronidase was expressed at therapeutic levels in the appropriate organelle and corrected the metabolic defect in cells exhibiting the characteristic pathology of this lysosomal storage disorder.

Original languageEnglish
Pages (from-to)2877-2881
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number8
StatePublished - Apr 1 1990
Externally publishedYes

Fingerprint

Mucopolysaccharidosis VII
Glucuronidase
Canidae
Genes
Glycosaminoglycans
Retinal Pigments
Bone Marrow Cells
Organelles
Complementary DNA
Fibroblasts
Epithelial Cells
Pathology

Keywords

  • β-glucuronidase
  • Animal models
  • Gene therapy
  • Lysosomal storage diseases
  • Substrate degradation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Restoration of normal lysosomal function in mucopolysaccharidosis type VII cells by retroviral vector-mediated gene transfer. / Wolfe, John H.; Schuchman, Edward H.; Stramm, Lawrence E.; Concaugh, Elizabeth A.; Haskins, Mark E.; Aguirre, Gustavo D.; Patterson, Donald F.; Desnick, Robert J.; Gilboa, Eli.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 87, No. 8, 01.04.1990, p. 2877-2881.

Research output: Contribution to journalArticle

Wolfe, JH, Schuchman, EH, Stramm, LE, Concaugh, EA, Haskins, ME, Aguirre, GD, Patterson, DF, Desnick, RJ & Gilboa, E 1990, 'Restoration of normal lysosomal function in mucopolysaccharidosis type VII cells by retroviral vector-mediated gene transfer', Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 8, pp. 2877-2881.
Wolfe, John H. ; Schuchman, Edward H. ; Stramm, Lawrence E. ; Concaugh, Elizabeth A. ; Haskins, Mark E. ; Aguirre, Gustavo D. ; Patterson, Donald F. ; Desnick, Robert J. ; Gilboa, Eli. / Restoration of normal lysosomal function in mucopolysaccharidosis type VII cells by retroviral vector-mediated gene transfer. In: Proceedings of the National Academy of Sciences of the United States of America. 1990 ; Vol. 87, No. 8. pp. 2877-2881.
@article{755d8e2ce6074257bb467b5cb97b606c,
title = "Restoration of normal lysosomal function in mucopolysaccharidosis type VII cells by retroviral vector-mediated gene transfer",
abstract = "Retroviral vectors were constructed containing a rat β-glucuronidase cDNA driven by heterologous promoters. Vector-mediated gene transfer into human and canine β-glucuronidase-deficient mucopolysaccharidosis type VII fibroblasts completely corrected the deficiency in β-glucuronidase enzymatic activity. In primary cultures of canine mucopolysaccharidosis type VII retinal pigment epithelial cells, which contain large amounts of undegraded glycosaminoglycan substrates, vector correction restored normal processing of specific glycosaminoglycans in the lysosomal compartment. In canine mucopolysaccharidosis type VII bone marrow cells, β-glucuronidase was expressed at high levels in transduced cells. Thus, the vector-encoded β-glucuronidase was expressed at therapeutic levels in the appropriate organelle and corrected the metabolic defect in cells exhibiting the characteristic pathology of this lysosomal storage disorder.",
keywords = "β-glucuronidase, Animal models, Gene therapy, Lysosomal storage diseases, Substrate degradation",
author = "Wolfe, {John H.} and Schuchman, {Edward H.} and Stramm, {Lawrence E.} and Concaugh, {Elizabeth A.} and Haskins, {Mark E.} and Aguirre, {Gustavo D.} and Patterson, {Donald F.} and Desnick, {Robert J.} and Eli Gilboa",
year = "1990",
month = "4",
day = "1",
language = "English",
volume = "87",
pages = "2877--2881",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "8",

}

TY - JOUR

T1 - Restoration of normal lysosomal function in mucopolysaccharidosis type VII cells by retroviral vector-mediated gene transfer

AU - Wolfe, John H.

AU - Schuchman, Edward H.

AU - Stramm, Lawrence E.

AU - Concaugh, Elizabeth A.

AU - Haskins, Mark E.

AU - Aguirre, Gustavo D.

AU - Patterson, Donald F.

AU - Desnick, Robert J.

AU - Gilboa, Eli

PY - 1990/4/1

Y1 - 1990/4/1

N2 - Retroviral vectors were constructed containing a rat β-glucuronidase cDNA driven by heterologous promoters. Vector-mediated gene transfer into human and canine β-glucuronidase-deficient mucopolysaccharidosis type VII fibroblasts completely corrected the deficiency in β-glucuronidase enzymatic activity. In primary cultures of canine mucopolysaccharidosis type VII retinal pigment epithelial cells, which contain large amounts of undegraded glycosaminoglycan substrates, vector correction restored normal processing of specific glycosaminoglycans in the lysosomal compartment. In canine mucopolysaccharidosis type VII bone marrow cells, β-glucuronidase was expressed at high levels in transduced cells. Thus, the vector-encoded β-glucuronidase was expressed at therapeutic levels in the appropriate organelle and corrected the metabolic defect in cells exhibiting the characteristic pathology of this lysosomal storage disorder.

AB - Retroviral vectors were constructed containing a rat β-glucuronidase cDNA driven by heterologous promoters. Vector-mediated gene transfer into human and canine β-glucuronidase-deficient mucopolysaccharidosis type VII fibroblasts completely corrected the deficiency in β-glucuronidase enzymatic activity. In primary cultures of canine mucopolysaccharidosis type VII retinal pigment epithelial cells, which contain large amounts of undegraded glycosaminoglycan substrates, vector correction restored normal processing of specific glycosaminoglycans in the lysosomal compartment. In canine mucopolysaccharidosis type VII bone marrow cells, β-glucuronidase was expressed at high levels in transduced cells. Thus, the vector-encoded β-glucuronidase was expressed at therapeutic levels in the appropriate organelle and corrected the metabolic defect in cells exhibiting the characteristic pathology of this lysosomal storage disorder.

KW - β-glucuronidase

KW - Animal models

KW - Gene therapy

KW - Lysosomal storage diseases

KW - Substrate degradation

UR - http://www.scopus.com/inward/record.url?scp=0025239382&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025239382&partnerID=8YFLogxK

M3 - Article

C2 - 2158095

AN - SCOPUS:0025239382

VL - 87

SP - 2877

EP - 2881

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 8

ER -