A new transgene reporter for in vivo magnetic resonance imaging.
We report a new platform technology for visualizing transgene expression in living subjects using magnetic resonance imaging (MRI). Using a vector, we introduced an MRI reporter, a metalloprotein from the ferritin family, into specific host tissues. The reporter is made superparamagnetic as the cell sequesters endogenous iron from the organism. In this new approach, the cells construct the MRI contrast agent in situ using genetic instructions introduced by the vector. No exogenous metal-complexed contrast agent is required, thereby simplifying intracellular delivery. We used a replication-defective adenovirus vector to deliver the ferritin transgenes. Following focal inoculation of the vector into the mouse brain, we monitored the reporter activity using in vivo time-lapse MRI. We observed robust contrast in virus-transduced neurons and glia for several weeks. This technology is adaptable to monitor transgene expression in vivo in many tissue types and has numerous biomedical applications, such as visualizing preclinical therapeutic gene delivery.
Genove
Guillem
G
Department of Biological Sciences and Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA.
DeMarco
Ulrike
U
Xu
Hongyan
H
Goins
William F
WF
Ahrens
Eric T
ET
D000256:Adenoviridae; D000818:Animals; D001921:Brain; D002478:Cells, Cultured; D003673:Defective Viruses; D005293:Ferritins / Q000235:genetics; D015870:Gene Expression; D017930:Genes, Reporter; D005822:Genetic Vectors; D007501:Iron; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D014161:Transduction, Genetic; D019076:Transgenes
D005293:Ferritins; D007501:Iron