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Human Erythropoietin Gene Delivery Using an Arginine-Grafted Bioreducible Polymer System

Title
Human Erythropoietin Gene Delivery Using an Arginine-Grafted Bioreducible Polymer System
Author
이민형
Keywords
Anemia; therapy; Animals; Arginine; DNA; genetics; Erythrocytes; metabolism; Erythropoiesis; Erythropoietin; biosynthesis; Gene Transfer Techniques; Genetic Therapy
Issue Date
2012-07
Publisher
The American Society of Gene & Cell Therapy
Citation
Molecular therapy : the journal of the American Society of Gene Therapy, 2012, 20(7), P.1360~1366
Abstract
Erythropoiesis-stimulating agents are widely used to treat anemia for chronic kidney disease (CKD) and cancer, however, several clinical limitations impede their effectiveness. Nonviral gene therapy systems are a novel solution to these problems as they provide stable and low immunogenic protein expression levels. Here, we show the application of an arginine-grafted bioreducible poly(disulfide amine) (ABP) polymer gene delivery system as a platform for in vivo transfer of human erythropoietin plasmid DNA (phEPO) to produce long-term, therapeutic erythropoiesis. A single systemic injection of phEPO/ABP polyplex led to higher hematocrit levels over a 60-day period accompanied with reticulocytosis and high hEPO protein expression. In addition, we found that the distinct temporal and spatial distribution of phEPO/ABP polyplexes contributed to increased erythropoietic effects compared to those of traditional EPO therapies. Overall, our study suggests that ABP polymer-based gene therapy provides a promising clinical strategy to reach effective therapeutic levels of hEPO gene.
URI
http://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(16)32565-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1525001616325655%3Fshowall%3Dtruehttp://hdl.handle.net/20.500.11754/67234
ISSN
1525-0016
DOI
10.1038/mt.2012.62
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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