Heparin-coated superparamagnetic nanoparticle-mediated adeno-associated virus delivery for enhancing cellular transduction
Autor: | Jae Hyung Jang, Eunmi Kim, Jun Ho Hwang, Slgirim Lee, Ik Sung Ahn, Chang Ha Lee, Jung Suk Kim |
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Rok vydání: | 2011 |
Předmět: |
Cell Survival
viruses Genetic enhancement Genetic Vectors Pharmaceutical Science Biology Gene delivery medicine.disease_cause PC12 Cells Virus Viral vector Transduction (genetics) Transduction Genetic Nerve Growth Factor Neurites medicine Animals Humans Magnetite Nanoparticles Adeno-associated virus Heparin HEK 293 cells Gene Transfer Techniques Genetic Therapy Dependovirus Molecular biology Rats Cell biology HEK293 Cells Cell culture human activities |
Zdroj: | International Journal of Pharmaceutics. 421:397-404 |
ISSN: | 0378-5173 |
Popis: | Superparamagnetic iron oxide nanoparticles (SPIONs) have been exploited as an elegant vehicle to enhance gene delivery efficiencies in gene therapy applications. We developed a magnetically guided adeno-associated virus (AAV) delivery system for enhancing gene delivery to HEK293T and PC12 cell lines. Wild-type AAV2 and a novel AAV vector, AAVr3.45, which was directly evolved in a previous study to possess diverse cell tropisms, were used as gene carriers. Additionally, the affinity of each viral vector to heparin was employed as a moiety to immobilize virus onto heparin-coated SPIONs (HpNPs). Magnetically guided AAV delivery resulted fast and efficient cellular transduction. Importantly, a short exposure of virus to target cells under a magnetic field (180min) yielded comparable transduction produced by the conventional gene-delivery protocol (i.e., 24h-incubation of virus with target cells prior to replacing with fresh medium). Additionally, magnetic guidance of AAV encoding nerve growth factor (NGF) produced sufficient functional NGF, leading to robust neurite elongation by PC12 as compared to direct NGF protein delivery or non-magnetic delivery. The successful establishment of a magnetically guided AAV delivery system, with the ability to efficiently and rapidly infect target cells, will provide a powerful platform for a variety of gene therapy applications. |
Databáze: | OpenAIRE |
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