Prolonged Expression of Secreted Enzymes in Dogs After Liver-Directed Delivery of Sleeping Beauty Transposons: Implications for Non-Viral Gene Therapy of Systemic Disease
| Autor: | Elena L. Aronovich, Myra Rusten, Jason B. Bell, Bryan C. Hall, David W. Hunter, N. Matthew Ellinwood, R. Scott McIvor, Erik R. Olson, Perry B. Hackett, Kendra A. Hyland |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Systemic disease medicine.medical_treatment Mucopolysaccharidosis Transgene Gene Expression Transposases Gadolinium Pharmacology Biology Hemophilia A Immunomodulation 03 medical and health sciences Iduronidase Immune system Dogs Genes Reporter Gene expression Genetics medicine Animals Transgenes Molecular Biology Transposase Glucuronidase Gene Transfer Techniques Immunosuppression Genetic Therapy medicine.disease Mice Inbred C57BL 030104 developmental biology Liver Immunology DNA Transposable Elements Molecular Medicine |
| Zdroj: | Human gene therapy. 28(7) |
| ISSN: | 1557-7422 |
| Popis: | The non-viral, integrating Sleeping Beauty (SB) transposon system is efficient in treating systemic monogenic disease in mice, including hemophilia A and B caused by deficiency of blood clotting factors and mucopolysaccharidosis types I and VII caused by α-L-iduronidase (IDUA) and β-glucuronidase (GUSB) deficiency, respectively. Modified approaches of the hydrodynamics-based procedure to deliver transposons to the liver in dogs were recently reported. Using the transgenic canine reporter secreted alkaline phosphatase (cSEAP), transgenic protein in the plasma was demonstrated for up to 6 weeks post infusion. This study reports that immunosuppression of dogs with gadolinium chloride (GdCl3) prolonged the presence of cSEAP in the circulation up to 5.5 months after a single vector infusion. Transgene expression declined gradually but appeared to stabilize after about 2 months at approximately fourfold baseline level. Durability of transgenic protein expression in the plasma was inversely associated with trans... |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|