The authors thank the National Institutes of Health EB-11687 (MW); RR-02584 and CA-115531 (ADS); HL083194 (DNS), Oregon Nanoscience and Microtechnologies Institute, Portland State University, the Oregon Opportunity partnership for advancing biomedical research, the M.J. Murdock Charitable Trust and the Robert A Welch Foundation (AT-584) for financial support.
Organic & Biomolecular Chemistry
Gene therapy, Contrast media (Diagnostic imaging), Magnetic resonance imaging, Reporter genes, Transfection
Gene therapy is a potentially powerful treatment approach that targets molecular remedies for disease. Among other challenges it remains difficult to monitor gene delivery and its downstream metabolic consequences. Approaches to MRI gene reporters have been reported but few have the potential for translation beyond isolated cell systems. Herein, we report a polycationic polymer MRI contrast agent that binds to DNA in a ratio of one monomer unit per phosphate group of DNA. Significantly, this binding event diminishes the MR contrast signal from the agent itself potentially providing a platform for imaging delivery and release of a gene into cells and tissues. Importantly, we demonstrate here the proof of concept that a positively charged polymeric contrast agent can also act as a transfection agent, delivering the gene for encoding green fluorescent protein into cells. These observations provide support for the radical, new idea of creating a combined transfection/imaging agent for monitoring gene delivery in real time by MRI.
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Published as: Wu, Y., Carney, C. E., Denton, M., Hart, E., Zhao, P., Streblow, D. N., Sherry, A. D., & Woods, M. (2010). Polymeric PARACEST MRI contrast agents as potential reporters for gene therapy. Organic & biomolecular chemistry, 8(23), 5333–5338. https://doi.org/10.1039/c0ob00087f