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

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 β-glucuronidase. One to six lattices each containing 109 skin fibroblasts were implanted into the omentum of the donor animal. Laparotomies performed at regular intervals showed vascularized neo-organs without local inflammation. Human β-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.

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Moullier, P., Bohl, D., Cardoso, J. et al. Long-term delivery of a lysosomal enzyme by genetically modified fibroblasts in dogs. Nat Med 1, 353–357 (1995). https://doi.org/10.1038/nm0495-353

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