Polymeric PARACEST MRI contrast agents as potential reporters for gene therapy.
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.
Wu
Yunkou
Y
Department of Chemistry, University of Texas at Dallas, P.O. Box 830668, Richardson, Texas 75083, USA.
Carney
Christiane E
CE
Denton
Michael
M
Hart
Elaine
E
Zhao
Piyu
P
Streblow
Daniel N
DN
Sherry
A Dean
AD
Woods
Mark
M
D000818:Animals; D003287:Contrast Media / Q000737:chemistry*; D015316:Genetic Therapy; D057809:HEK293 Cells; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D015394:Molecular Structure; D011073:Polyamines / Q000737:chemistry*; D000071228:Polyelectrolytes; D011108:Polymers / Q000737:chemistry*; D012474:Salmon
D003287:Contrast Media; D011073:Polyamines; D000071228:Polyelectrolytes; D011108:Polymers