Issue 23, 2010
From the journal:

Organic & Biomolecular Chemistry

Polymeric PARACEST MRI contrast agents as potential reporters for gene therapy†

Yunkou Wu,a   Christiane E. Carney,b   Michael Denton,c   Elaine Hart,c   Piyu Zhao,a   Daniel N. Streblow,c   A. Dean Sherryad  and  Mark Woods*be  

* Corresponding authors

a Department of Chemistry, University of Texas at Dallas, P.O. Box 830668, Richardson, Texas, USA

b Department of Chemistry, Portland State University, P.O. Box 751, Portland, OR 97207, USA
E-mail: mark.woods@pdx.edu
Fax: + 1 503 725 9525
Tel: + 1 503 725 8238

c Vaccine and Gene Therapy Institute, Oregon Health and Sciences University, 505 NW 185th Avenue, Beaverton, Oregon 97006, USA

d Advanced Imaging Research Center, University of Texas Southwestern Medical Center, 5325 Harry Hines Blvd, Dallas, Texas 75235, USA

e Advanced Imaging Research Center, Oregon Health and Sciences University, 3181 S.W. Sam Jackson Park Road, L452, Portland, Oregon 97239, USA
E-mail: woodsmar@ohsu.edu
Fax: + 1 503 418 1543
Tel: + 1 503 418 5530

Abstract

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.

Graphical abstract: Polymeric PARACEST MRI contrast agents as potential reporters for gene therapy

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Article information

DOI
https://doi.org/10.1039/C0OB00087F
Article type
Paper
Submitted
06 May 2010
Accepted
09 Aug 2010
First published
16 Sep 2010

Org. Biomol. Chem., 2010,8, 5333-5338

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Polymeric PARACEST MRI contrast agents as potential reporters for gene therapy

Y. Wu, C. E. Carney, M. Denton, E. Hart, P. Zhao, D. N. Streblow, A. D. Sherry and M. Woods, Org. Biomol. Chem., 2010, 8, 5333 DOI: 10.1039/C0OB00087F

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