Long-term delivery of a lysosomal enzyme by genetically modified fibroblasts in dogs

Nat Med. 1995 Apr;1(4):353-7. doi: 10.1038/nm0495-353.

Abstract

We have evaluated the feasibility and efficacy of intraperitoneal implants (neo-organs) for protein delivery in large animals. Skin biopsies were taken from four healthy dogs. Primary fibroblast cultures were transduced with a retroviral vector coding for the human beta-glucuronidase. One to six lattices each containing 10(9) skin fibroblasts were implanted into the omentum of the donor animal. Laparotomies performed at regular intervals showed vascularized neo-organs without local inflammation. Human beta-glucuronidase levels equivalent to 0.8 to 3.1% of the endogenous canine activity were detected for up to 340 days on liver biopsy samples. These results indicate that neo-organs can be considered for the long-term delivery of therapeutic proteins or enzymes in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Collagen
  • DNA / analysis
  • Dogs
  • Drug Delivery Systems*
  • Electrophoresis, Polyacrylamide Gel
  • Feasibility Studies
  • Fibroblasts / enzymology
  • Fibroblasts / transplantation*
  • Genetic Therapy / methods
  • Genetic Vectors
  • Glucuronidase / administration & dosage
  • Glucuronidase / genetics
  • Glucuronidase / metabolism*
  • Histocytochemistry
  • Liver / enzymology
  • Lysosomes / enzymology*
  • Omentum
  • Peritoneal Cavity
  • Prostheses and Implants*
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Retroviridae / genetics
  • Skin / cytology
  • Spleen / enzymology

Substances

  • Recombinant Fusion Proteins
  • Collagen
  • DNA
  • Glucuronidase