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Magnetic Nanoparticles Enhance Adenovirus Transduction In Vitro and In Vivo

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ABSTRACT

Purpose

Adenoviruses are among the most powerful gene delivery systems. Even if they present low potential for oncogenesis, there is still a need for minimizing widespread delivery to avoid deleterious reactions. In this study, we investigated Magnetofection efficiency to concentrate and guide vectors for an improved targeted delivery.

Method

Magnetic nanoparticles formulations were complexed to a replication defective Adenovirus and were used to transduce cells both in vitro and in vivo. A new integrated magnetic procedure for cell sorting and genetic modification (i-MICST) was also investigated.

Results

Magnetic nanoparticles enhanced viral transduction efficiency and protein expression in a dose-dependent manner. They accelerated the transduction kinetics and allowed non-permissive cells infection. Magnetofection greatly improved adenovirus-mediated DNA delivery in vivo and provided a magnetic targeting. The i-MICST results established the efficiency of magnetic nanoparticles assisted viral transduction within cell sorting columns.

Conclusion

The results showed that the combination of Magnetofection and Adenoviruses represents a promising strategy for gene therapy. Recently, a new integrated method to combine clinically approved magnetic cell isolation devices and genetic modification was developed. In this study, we validated that magnetic cell separation and adenoviral transduction can be accomplished in one reliable integrated and safe system.

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ACKNOWLEDGMENTS & DISCLOSURES

This research was supported by the European Union through the following projects: FP6-LIFESCIHEALTH Project “Magselectofection” Contract LSHB-CT-2006-19038; FP6-LIFESCIHEALTH Project “Epicure” Contract LSHM-CT-2006-037315 and FP7 EU-Project: Project “GAMBA” Contract NMP3-SL-2010-245993.

C.S., N.L., F.S. and O.Z. are employed by OZ Biosciences, which manufactures and distributes the AdenoMag and Viro-MICST products.

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  1. OZ Biosciences, Parc Scientifique de Luminy, 163 Avenue de Luminy case 922, 13288, Marseille cedex 9, France

    Cédric Sapet, Nicolas Laurent, Flavie Sicard & Olivier Zelphati

  2. INSERM UMR S901, Institut de Neurobiologie de la Méditerranée (INMED), Parc Scientifique de Luminy, 163 route de Luminy - BP13, 13273, Marseille cedex 09, France

    Christophe Pellegrino

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  1. Cédric Sapet
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Correspondence to Cédric Sapet or Olivier Zelphati.

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Sapet, C., Pellegrino, C., Laurent, N. et al. Magnetic Nanoparticles Enhance Adenovirus Transduction In Vitro and In Vivo . Pharm Res 29, 1203–1218 (2012). https://doi.org/10.1007/s11095-011-0629-9

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