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Vol. 39, No. 1, 2007
Issue release date: March 2007
Section title: Original Paper
Eur Surg Res 2007;39:23–34
(DOI:10.1159/000098437)

Development of Gene Vectors for Pinpoint Targeting to Human Hepatocytes by Cationically Modified Polymer Complexes

Chiba N. · Ueda M. · Shimada T. · Jinno H. · Watanabe J. · Ishihara K. · Kitajima M.
aDepartment of Surgery, Keio University School of Medicine, and bDepartment of Material Engineering, School of Engineering, University of Tokyo, Tokyo, Japan

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 9/13/2006
Published online: 1/8/2007

Number of Print Pages: 12
Number of Figures: 8
Number of Tables: 1

ISSN: 0014-312X (Print)
eISSN: 1421-9921 (Online)

For additional information: http://www.karger.com/ESR

Abstract

We developed a vector that might enable gene therapy of metabolic liver disease or hepatoma. Here we demonstrate the use of cationically modified biocompatible phospholipid polymer conjugated with hepatitis B surface (HBs) antigen for the specific transfer of genes into human hepatocytes. Poly(2-methacryloyloxyethyl phosphorylcholine (MPC)- co-N,N-dimethylaminoethyl methacrylate (DMAEMA)-co- p-nitrophenylcarbonyloxyethyl methacrylate(NPMA))(polyMDN) was prepared as a frame of vector. The specific expression of sFlt-1 or GFP by polyMDN conjugated with HBs containing plasmid (plasmid/polyMDN-HBs), polyMDN containing plasmid (plasmid/polyMDN), plasmid only and PBS were assessed in tumor cells (HepG2 or WiDr) in vitro and in vivo. The histological findings, organ weight changes, and degree of liver dysfunction were examined in the mice administered by several reagents. The sFlt-1 and GFP expression was observed only in the HepG2 cells transfected with sFlt-1 or GFP/polyMDN-HBs. None of the side effects mentioned above was observed. In conclusion, these results suggest that polyMDN-HBs is a human hepatocyte-specific gene delivery vector that might not have serious side effects.


  

Author Contacts

Masakazu Ueda
Department of Surgery
Keio University School of Medicine, 35 Shinanomachi
Shinjuku-ku, 160-8582 Tokyo (Japan)
Tel. +81 3 3353 1211, ext. 62334, Fax +81 3 3355 4707, E-Mail m_ueda@sc.itc.keio.ac.jp

  

Article Information

Received: May 11, 2006
Accepted after revision: September 13, 2006
Published online: January 8, 2007
Number of Print Pages : 12
Number of Figures : 8, Number of Tables : 1, Number of References : 35

  

Publication Details

European Surgical Research (Clinical and Experimental Surgery)

Vol. 39, No. 1, Year 2007 (Cover Date: March 2007)

Journal Editor: Kempski, O. (Mainz)
ISSN: 0014–312X (print), 1421–9921 (Online)

For additional information: http://www.karger.com/ESR


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 9/13/2006
Published online: 1/8/2007

Number of Print Pages: 12
Number of Figures: 8
Number of Tables: 1

ISSN: 0014-312X (Print)
eISSN: 1421-9921 (Online)

For additional information: http://www.karger.com/ESR


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