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Magnetic resonance imaging of viral particle biodistribution in vivo

Abstract

We describe here a technique for the visualization of viral vector delivery by magnetic resonance imaging (MRI) in vivo. By conjugating avidin-coated baculoviral vectors (Baavi) with biotinylated ultra-small superparamagnetic iron oxide particles (USPIO), we are able to produce vector-related MRI contrast in the choroid plexus cells of rat brain in vivo over a period of 14 days. Ten microlitres of 2.5 × 1010 PFU/ml nuclear-targeted LacZ-encoding Baavi with bUSPIO coating was injected into rat brain ventricles and visualized by MRI at 4.7 T. As baculoviruses exhibit restricted cell-type specificity in the rat brain, altered MRI contrast was detected in the choroid plexus of the injected ventricles. No specific signal loss was detected when wild-type baculoviruses or intact biotinylated USPIO particles were injected into the lateral ventricles. Cryosectioned brains were stained for nuclear-targeted β-galactosidase gene expression, which was found to colocalize with MRI contrast. This study provides the first proof of principle for robust and non-invasive viral vector MRI by using avidin-displaying viruses in vivo. Considering the widespread use of MRI in current medical imaging, the approach is likely to provide numerous future applications in imaging of therapeutic gene transfer.

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Acknowledgements

We thank the Finnish Academy (JH, SY), the Sigrid Juselius Foundation (JH, SY), Instrumentarium Science Foundation (JH, TL), Onion Science Foundation (TL) and Ark Therapeutics Ltd (JR, TW, KA) for support.

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Correspondence to J K Räty, S Ylä-Herttuala or J M Hakumäki.

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Räty, J., Liimatainen, T., Wirth, T. et al. Magnetic resonance imaging of viral particle biodistribution in vivo. Gene Ther 13, 1440–1446 (2006). https://doi.org/10.1038/sj.gt.3302828

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