Elastin-like polypeptide matrices for enhancing adeno-associated virus-mediated gene delivery to human neural stem cells
- Authors
- Kim, J-S; Chu, H. S.; Park, K. I.; Won, J-I; Jang, J-H
- Issue Date
- Mar-2012
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- elastin-like polypeptide; adeno-associated virus; gene delivery; substrate-mediated delivery
- Citation
- GENE THERAPY, v.19, no.3, pp.329 - 337
- Journal Title
- GENE THERAPY
- Volume
- 19
- Number
- 3
- Start Page
- 329
- End Page
- 337
- URI
- https://scholarworks.bwise.kr/hongik/handle/2020.sw.hongik/19009
- DOI
- 10.1038/gt.2011.84
- ISSN
- 0969-7128
- 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. Gene Therapy (2012) 19, 329-337; doi:10.1038/gt.2011.84; published online 9 June 2011
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