Development of gene vectors for pinpoint targeting to human hepatocytes by cationically modified polymer complexes

Naokazu Chiba, Masakazu Ueda, Toshiyuki Shimada, Hiromitsu Jinno, Junji Watanabe, Kazuhiko Ishihara, Masaki Kitajima

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)23-34
Number of pages12
JournalEuropean Surgical Research
Volume39
Issue number1
DOIs
Publication statusPublished - 2007 Mar 1

Keywords

  • Cationic polymer
  • Gene delivery
  • Gene vector
  • MPC polymer
  • Pinpoint targeting to the hepatocytes

ASJC Scopus subject areas

  • Surgery

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