Long-term delivery of a lysosomal enzyme by genetically modified fibroblasts in dogs.
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.
Moullier
P
P
Laboratoire Rétrovirus et Transfert Génétique, CNRS URA 1157, Institut Pasteur, Paris, France.
Bohl
D
D
Cardoso
J
J
Heard
J M
JM
Danos
O
O
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen; D004247:DNA / Q000032:analysis; D004285:Dogs; D016503:Drug Delivery Systems; D004591:Electrophoresis, Polyacrylamide Gel; D005240:Feasibility Studies; D005347:Fibroblasts / Q000201:enzymology / Q000637:transplantation*; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D005966:Glucuronidase / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D006651:Histocytochemistry; D008099:Liver / Q000201:enzymology; D008247:Lysosomes / Q000201:enzymology*; D009852:Omentum; D010529:Peritoneal Cavity; D019736:Prostheses and Implants; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D012867:Skin / Q000166:cytology; D013154:Spleen / Q000201:enzymology
D011993:Recombinant Fusion Proteins; D003094:Collagen; D004247:DNA; D005966:Glucuronidase