Ex vivo transduction of human dermal tissue structures for autologous implantation production and delivery of therapeutic proteins
| Autor: | Andrew L. Pearlman, Amos Panet, Joel Kaye, Yitzhak Lippin, Stephen F. Bellomo, Moni Shavit, Noga Langer, Daniel Afik, Einat Brill-Almon, Baruch S. Stern, Noam Shani |
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| Rok vydání: | 2005 |
| Předmět: |
Genetic Vectors
Mice SCID Biology Transplantation Autologous Adenoviridae Viral vector Mice Transduction (genetics) Dermis Transduction Genetic In vivo Drug Discovery medicine Genetics Animals Humans Erythropoietin Molecular Biology Pharmacology Expression vector Genetic Therapy Molecular biology Recombinant Proteins Cell biology Transplantation medicine.anatomical_structure Molecular Medicine Female Ex vivo medicine.drug |
| Zdroj: | Molecular Therapy. 12(2):274-282 |
| ISSN: | 1525-0016 |
| DOI: | 10.1016/j.ymthe.2005.03.023 |
| Popis: | Systemic delivery of therapeutic proteins through gene transfer approaches has been carried out mostly by ex vivo transduction of single cells or by direct in vivo injection of an expression vector. In this work an intact miniature biopsy of human dermis (microdermis) is harvested and transduced ex vivo by a viral vector encoding a gene for the therapeutic protein. The microdermis preserves its three-dimensional structure and viability during the ex vivo manipulations. Furthermore, upon transduction with adenoviral and adeno-associated viral vectors the microdermis secretes recombinant human erythropoietin (hEPO). Biochemical analysis of the secreted hEPO showed similarity to the clinically approved recombinant hEPO. Subcutaneous implantation of microdermal hEPO into SCID mice exhibited hEPO secretion in the blood circulation and preserved elevated hematocrit for several months, demonstrating the technology's potential for sustained delivery of protein therapeutics. |
| Databáze: | OpenAIRE |
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