Human erythropoietin gene delivery using an arginine-grafted bioreducible polymer system

Youngsook Lee, Hye Yeong Nam, Jaesung Kim, Minhyung Lee, James W. Yockman, Sug Kyun Shin, Sung Wan Kim

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish
Pages (from-to)1360-1366
Number of pages7
JournalMolecular Therapy
Volume20
Issue number7
DOIs
StatePublished - 2012 Jul

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    Lee, Y., Nam, H. Y., Kim, J., Lee, M., Yockman, J. W., Shin, S. K., & Kim, S. W. (2012). Human erythropoietin gene delivery using an arginine-grafted bioreducible polymer system. Molecular Therapy, 20(7), 1360-1366. https://doi.org/10.1038/mt.2012.62