MR imaging of gene delivery to the central nervous system with an artificial vector.
OBJECTIVE
To determine whether gene delivery by means of a synthetic no viral DNA delivery system that is capable of gene transfer can be mapped with magnetic resonance (MR) imaging.


METHODS
The DNA delivery system consisted of aminated (poly-L-lysine-conjugated) dextran chains anchored together with a central superparamagnetic core. Three different types of constructs were synthesized that differed in their amino content and, thus, DNA-loading capacity. The model plasmid consisted of complementary DNA encoding for humanized green fluorescent protein. Constructs were tested in cell culture and in vivo in a rat model.


RESULTS
All three constructs were capable of transfecting human cells in culture with transfection efficiencies ranging from 0.3% to 4.1%, which is similar to that of diethylaminoethyl-dextran. MR imaging experiments showed that DNA constructs induced signal intensity changes that co-localized with phosphorus-33-labeled plasmid distribution at autoradiography. After injection of the constructs into the corpus callosum of rats, weak green fluorescent protein expression of neuronal and glial cells could be detected at immunohistologic examination.


CONCLUSIONS
Dextran-based nonviral DNA delivery systems are capable of transfecting cells and can be visualized with MR imaging.
de Marco
G
G
Department of Radiology, Massachusetts General Hospital, Charlestown 02129, USA.
Bogdanov
A
A
Marecos
E
E
Moore
A
A
Simonova
M
M
Weissleder
R
R
D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D003337:Corpus Callosum / Q000378:metabolism; D003637:DEAE-Dextran / Q000737:chemistry; D018076:DNA, Complementary / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000737:chemistry; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D005819:Genetic Markers; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D010957:Plasmids; D011107:Polylysine / Q000737:chemistry; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
D000596:Amino Acids; D018076:DNA, Complementary; D003911:Dextrans; D005456:Fluorescent Dyes; D005819:Genetic Markers; D010761:Phosphorus Radioisotopes; D011506:Proteins; D019275:Radiopharmaceuticals; D011107:Polylysine; D003637:DEAE-Dextran