Non-invasive imaging using reporter genes altering cellular water permeability

Arnab Mukherjee, Di Wu, Hunter C. Davis and Mikhail G. Shapiro ()
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Arnab Mukherjee: California Institute of Technology
Di Wu: California Institute of Technology
Hunter C. Davis: California Institute of Technology
Mikhail G. Shapiro: California Institute of Technology

Nature Communications, 2016, vol. 7, issue 1, 1-9

Abstract: Abstract Non-invasive imaging of gene expression in live, optically opaque animals is important for multiple applications, including monitoring of genetic circuits and tracking of cell-based therapeutics. Magnetic resonance imaging (MRI) could enable such monitoring with high spatiotemporal resolution. However, existing MRI reporter genes based on metalloproteins or chemical exchange probes are limited by their reliance on metals or relatively low sensitivity. Here we introduce a new class of MRI reporters based on the human water channel aquaporin 1. We show that aquaporin overexpression produces contrast in diffusion-weighted MRI by increasing tissue water diffusivity without affecting viability. Low aquaporin levels or mixed populations comprising as few as 10% aquaporin-expressing cells are sufficient to produce MRI contrast. We characterize this new contrast mechanism through experiments and simulations, and demonstrate its utility in vivo by imaging gene expression in tumours. Our results establish an alternative class of sensitive, metal-free reporter genes for non-invasive imaging.

Date: 2016
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DOI: 10.1038/ncomms13891

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