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Novel receptor-mediated gene delivery system comprising plasmid/protamine/sugar-containing polyanion ternary complex

Paper ID Volume ID Publish Year Pages File Format Full-Text
12428 792 2004 7 PDF Available
Title
Novel receptor-mediated gene delivery system comprising plasmid/protamine/sugar-containing polyanion ternary complex
Abstract

Poly(ethylene glycol) (PEG) derivative having both carboxylic acid-, and lactose-side chains (Lac-PEG-C) deposited onto the surface of DNA/protamine (PRT) complex, and the self-assembled ternary complex was obtained. The diameter of the complexes was 180–200 nm, and they showed good size stability even in the high ionic strength solutions. Lac-PEG-C coating reduced their surface electric potential, and effectively avoided the albumin-induced aggregation. DNA/PRT/Lac-PEG-C complex did not coagulate the red blood cells, and their cytotoxicity evaluated by WST-1 was very low. Lac-PEG-C added to the plasmid/PRT complex prior to the incubation with HepG2 cells extremely enhanced the gene-expression, and by the plasmid/PRT/Lac-PEG-C complex prepared at 1:1.5:8 in weight, 56-fold higher expression of luciferase than that without Lac-PEG-C was observed. The treatment with asialofetuin or phenylarsine oxide evidently interfered with the gene-expression. The high gene expression by the plasmid/PRT/Lac-PEG-C ternary complex on the hepatocyte would be attributed to the asialoglycoprotein receptor-mediated endocytosis.

Keywords
Gene therapy; Protamine; Polyethylene glycol; Hepatocyte; Polyion complex
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 25, Issue 16, July 2004, Pages 3267–3273
Authors
, , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
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Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
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Full-text PDF Download
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