Receptor-targeted co-transport of DNA and magnetic resonance contrast agents.
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 co-transported. These protocols may allow non-invasive MRI monitoring of DNA delivery for gene therapy in real time.
Kayyem
J F
JF
Division of BIology, California Institute of Technology, Pasadena 91125, USA.
Kumar
R M
RM
Fraser
S E
SE
Meade
T J
TJ
D002478:Cells, Cultured; D003287:Contrast Media / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D019786:Gadolinium DTPA; D005819:Genetic Markers; D006801:Humans; D008279:Magnetic Resonance Imaging; D011107:Polylysine / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D014162:Transfection; D014168:Transferrin / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D003287:Contrast Media; D005819:Genetic Markers; D014168:Transferrin; D011107:Polylysine; D004247:DNA; D019786:Gadolinium DTPA