Receptor-targeted co-transport of DNA and magnetic resonance contrast agents
Abstract
Background: Ligand molecules conjugated to polylysine can be electrostatically bound to DNA and can bind receptors or antigens on the surface of cells, delivering the DNA into specific cells and tissues. Several researchers have used this approach to generate non-viral vehicles for the efficient delivery of DNA to specific cells. We have attempted to adopt this general approach to the cell-specific delivery of magnetic contrast agents for use in magnetic resonance imaging (MRI). Results: We have synthesized a new class of agents capable of both transfecting genes into cells and enhancing the contrast of the targeted cells for MRI. DNA is used both to encode a marker gene and as a molecular scaffold, which electrostatically binds polylysine conjugated to transferrin, an iron uptake protein, and polylysine modified with gadolinium chelated to diethylenetriaminepetaacetic acid. When cells displaying the transferrin receptor are treated with these particles, high levels of gene expression are observed, higher than with control particles composed only of transferrin, polylysine and DNA. The treated cells show specific MRI contrast enhancement, which did not require expression of the marker gene. Conclusions: The development of this class of particles permits the use of novel protocols by which genes for genetic therapy and agents for MRI contrast are cotransported. These protocols may allow non-invasive MRI monitoring of DNA delivery for gene therapy in real time.
Additional Information
© 1995 Elsevier Ltd. Received: 4 Aug 1995; revisions requested: 22 Aug 1995; revisions received: 1 Sep 1995. Accepted: 5 Sep 1995. The authors thank the Baxter Foundation for generous support of this work. We thank Pratik Gosh and Rex Moats for assistance with image acquisition and Kim Mislick for helpful discussions. R.M.K. was supported in part by a Summer Undergraduate Research Fellowship at Caltech.Additional details
- Eprint ID
- 65265
- DOI
- 10.1016/1074-5521(95)90126-4
- Resolver ID
- CaltechAUTHORS:20160310-135832264
- Baxter Foundation
- Caltech Summer Undergraduate Research Fellowship (SURF)
- Created
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2016-03-10Created from EPrint's datestamp field
- Updated
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2021-11-10Created from EPrint's last_modified field