Targeted transduction of cells/tissue in vivo

doi:10.1038/protex.2012.024

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Method Article

Targeted transduction of cells/tissue in vivo

Flavie Sicard, Mélanie Bertuzzi, Nicolas Laurent, Cédric Sapet, Elodie Bertosio

Flavie Sicard

OZ Biosciences

Corresponding Author

Mélanie Bertuzzi

OZ Biosciences

Nicolas Laurent

OZ Biosciences

Cédric Sapet

OZ Biosciences

Elodie Bertosio

OZ Biosciences

DOI:

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In vivo Magnetofection has been developed for in vivo targeted transduction with any viral vectors (In vivo ViroMag). Virus/nanoparticles can be easily administrated through various injection routes such as systemic administration (intravenous, intra-artery) or local administration (intraperitoneal, intratumoral, intracerebroventricular, intramuscular).

Keywords

In Vivo, Transduction, AAV, lentivirus, retrovirus, adenovirus

Figure 1

Figure 2

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supplement0.ppt
In vivo ViroMag – targeted viral infection icv Infection of rat embryo brain with adenovirus Sapet and coll. have shown that magnetic nanoparticles enhanced adenovirus transduction in vivo after intracerebroventricular injection (i.c.v.). Moreover, infection could be confined and directed towards the magnetic field. The uterine horns of pregnant rats [embryonic day 15] were exposed, and the third ventricle of each embryo was injected with Fast Green combined with Ad-GFP complexed to AdenoMag. When injected with AdenoMag, a magnet was applied for 30s following injection on one side of the embryo cranium. After injection, the uterine horns were replaced. Pictures show the third ventricle of E17 rat embryo (2 days post surgery). In brains non-exposed to magnet (A), the adenovirus-transduced cells are located on both side of the ventricle; cells are mainly restricted to this region indicating that the injection took place in this part of the brain. In brains exposed to magnetic field (B), the infected cells are located on one side of the ventricle due to the 30 s magnet-application represented by white arrow. From Sapet et al. Pharm Res 2011; (13).
supplement0.ppt
In vivo ViroMag – targeted viral infection icv Infection of rat embryo brain with lentivirus ViroMag magnetic nanoparticles associated with lentivirus have been used by Sapet and coll. to concentrate and target viral transduction in rat brain. Results showed a significant enhancement of gene expression with Magnetofection™ than with standard infection. Brain sections at 8 days after lateral ventricular injection of 109 particles of GFP-lentivirus coupled with ViroMag into in utero rat embryos (E16) showed a diffuse GFP expression (in green) due to a widespread infection of neurons (A). The association of GFP-lentivirus with ViroMag induced a targeted local area as shown by the GFP expression in neurons lying under a magnet at the surface of the embryo skull (B). A more intense and restricted GFP-expression (C) was also observed when the magnet was positioned on the edge of the brain leading to an accumulation of viral particles and infected neurons in the focal area. From Sapet et al. ; Drug Delivery Technol., 201010:24-29 (14). The results present the high efficiency of In vivo ViroMag for targeted delivery of viral vector after intracerebroventricular injection