Highly efficient in vivo gene transfection by plasmid/PEI complexes coated by anionic PEG derivatives bearing carboxyl groups and RGD peptide.
A new class of an anionic poly (ethylene glycol) derivative, PEG-Suc, bearing 17.7 pairs of carboxylic acid-side chains was synthesized. PEG-Suc deposited onto the DNA/polyethyleneimine complexes without destroying them even at high dose ratio. Coating of the DNA complexes by PEG-Suc recharged their surface to negative, and effectively protected them from the albumin-induced aggregation. Paired carboxyl groups in the side chains showed higher proton sponge effect. Negatively charged surface would diminish the electrostatic binding of the complexes to the cells, and the transfection efficiency on the cultured cells was not high. RGD peptide side chain as a ligand to malignant cell surfaces was then introduced to compensate the reduced electrical adhesion. RGD-PEG-Suc-coated plasmid/PEI complex brought about more than 3 times higher reporter protein activity on the cultured B16 cells. Those bio-compatible DNA complexes with ligand attained very high gene expression in tumor, lung, and liver after injection into mouse tail vein.
Sakae
Mitsuko
M
Department of Textile Science, Otsuma Women's University, Chiyoda-ku, Tokyo, Japan.
Ito
Tomoko
T
Yoshihara
Chieko
C
Iida-Tanaka
Naoko
N
Yanagie
Hironobu
H
Eriguchi
Masazumi
M
Koyama
Yoshiyuki
Y
D000818:Animals; D000838:Anions; D002264:Carboxylic Acids / Q000737:chemistry*; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004563:Electrochemistry; D015316:Genetic Therapy / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D009842:Oligopeptides / Q000737:chemistry*; D010316:Particle Size; D010957:Plasmids; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D011199:Potentiometry; D011522:Protons; D014162:Transfection
D000838:Anions; D002264:Carboxylic Acids; D009842:Oligopeptides; D011522:Protons; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D011094:Polyethyleneimine; D004247:DNA