Quantification of HSV-1-mediated expression of the ferritin MRI reporter in the mouse brain

Abstract

The development of effective strategies for gene therapy has been hampered by difficulties verifying transgene delivery in vivo and quantifying gene expression non-invasively. Magnetic resonance imaging (MRI) offers high spatial resolution and three-dimensional views, without tissue depth limitations. The iron-storage protein ferritin is a prototype MRI gene reporter. Ferritin forms a paramagnetic ferrihydrite core that can be detected by MRI via its effect on the local magnetic field experienced by water protons. In an effort to better characterize the ferritin reporter for central nervous system applications, we expressed ferritin in the mouse brain in vivo using a neurotropic herpes simplex virus type 1 (HSV-1). We computed three-dimensional maps of MRI transverse relaxation rates in the mouse brain with ascending doses of ferritin-expressing HSV-1. We established that the transverse relaxation rates correlate significantly to the number of inoculated infectious particles. Our results are potentially useful for quantitatively assessing limitations of ferritin reporters for gene therapy applications.

Tracking Neural Progenitor Cell Migration in the Rodent Brain Using Magnetic Resonance Imaging

“…A follow-up study used the neurotrophic HSV virus, which was thought to target neurons selectively over glia. In this study, the amount of signal correlated with the amount of virus injected, and this study supports the use of the ferritin as a means to quantify gene delivery in nucleic acid based therapies, rather than a method for tracking the migration of individual transfected neurons (Iordanova et al, 2013). Further modifications to the genetic construct may offer more functionality, and toward this end, inducible ferritin constructs have been used in culture to monitor the differentiation of mesenchymal stem cells into neural cells (Song et al, 2015).…”

Overexpression of the MRI Reporter Genes Ferritin and Transferrin Receptor Affect Iron Homeostasis and Produce Limited Contrast in Mesenchymal Stem Cells

“…We have generated mesenchymal stem cells expressing TfR1 , Fth1 or a combination of these two transgenes with the aim of exploring how each of those iron regulatory genes can impact iron homeostasis and T 2 contrast in an MSC cell line. The use of these genes has been previously explored in the literature, but the vast majority of the reports involve cancer cell lines [ 14 , 15 , 16 , 17 , 21 , 22 , 23 , 24 , 25 ] that have a physiology different to stem cells. Furthermore, previous studies have not addressed if overexpression of TfR1 can have any impact on the expression levels of other iron regulatory proteins.…”

Nanocatalysts‐Augmented and Photothermal‐Enhanced Tumor‐Specific Sequential Nanocatalytic Therapy in Both NIR‐I and NIR‐II Biowindows

“…Notably, compared to the intratumoral administration, the intravenous injection of Fe 3 O 4 @PPy@GOD NCs resulted in weaker but uniform signal distribution inside the entire tumor in T 2 MR images, indicating that the intravenous injection of Fe 3 O 4 @PPy@GOD NCs could reach the whole tumor region from blood circulation. Although MR imaging can monitor the whole body without the tissue‐depth limitation, the sensitivity and spatial resolution are the thresholds . PA imaging is not good at the whole‐body imaging, but it could offer higher spatial resolution and also be able to illustrate the detailed tumor microstructures (e.g., vasculature structures) .…”