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Elastin-like polypeptide matrices for enhancing adeno-associated virus-mediated gene delivery to human neural stem cells

Gene Therapy volume 19, pages 329–337 (2012)Cite this article

Abstract

The successful development of efficient and safe gene delivery vectors continues to be a major obstacle to gene delivery in stem cells. In this study, we have developed an elastin-like polypeptide (ELP)-mediated adeno-associated virus (AAV) delivery system for transducing fibroblasts and human neural stem cells (hNSCs). AAVs have significant promise as therapeutic vectors because of their safety and potential for use in gene targeting in stem cell research. ELP has been recently employed as a biologically inspired ‘smart’ biomaterial that exhibits an inverse temperature phase transition, thereby demonstrating promise as a novel drug carrier. The ELP that was investigated in this study was composed of a repetitive penta-peptide with [Val-Pro-Gly-Val-Gly]. A novel AAV variant, AAV r3.45, which was previously engineered by directed evolution to enhance transduction in rat NSCs, was nonspecifically immobilized onto ELPs that were adsorbed beforehand on a tissue culture polystyrene surface (TCPS). The presence of different ELP quantities on the TCPS led to variations in surface morphology, roughness and wettability, which were ultimately key factors in the modulation of cellular transduction. Importantly, with substantially reduced viral quantities compared with bolus delivery, ELP-mediated AAV delivery significantly enhanced delivery efficiency in fibroblasts and hNSCs, which have great potential for use in tissue engineering applications and neurodegenerative disorder treatments, respectively. The enhancement of cellular transduction in stem cells, as well as the feasibility of ELPs for utilization in three-dimensional scaffolds, will contribute to the advancement of gene therapy for stem cell research and tissue regenerative medicine.

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Acknowledgements

This work was supported by a National Research Foundation (NRF) grant funded by the Korean government (MEST) through the Active Polymer Center for Pattern Integration (No. R11-2007-050-00000-0) and NRF-20100015515. Additionally, this work was supported by the Human Resources Development of the Korea Institute of Energy Technology Evaluation and Planning (KETEP) grant funded by the Korea government Ministry of Knowledge Economy (No. 20104010100500). KIP was supported by the Stem Cell Research Center, Healthcare Technology R&D Project (A091159), and National Research Foundation of Korea grant (2010-0020289) by Korean Government.

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Authors and Affiliations

  1. Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul, Korea

    J-S Kim & J-H Jang

  2. School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea

    H S Chu

  3. Department of Pediatrics and BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea

    K I Park

  4. Department of Chemical Engineering, Hongik University, Seoul, Korea

    J-I Won

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Correspondence to J-I Won or J-H Jang.

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Kim, JS., Chu, H., Park, K. et al. Elastin-like polypeptide matrices for enhancing adeno-associated virus-mediated gene delivery to human neural stem cells. Gene Ther 19, 329–337 (2012). https://doi.org/10.1038/gt.2011.84

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