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Self-assemble gene delivery system for molecular targeting using nucleic acid aptamer
Authors:Kurosaki Tomoaki  Higuchi Norihide  Kawakami Shigeru  Higuchi Yuriko  Nakamura Tadahiro  Kitahara Takashi  Hashida Mitsuru  Sasaki Hitoshi
Affiliation:
  • a Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
  • b Global COE program, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
  • c Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan
  • d Institute of Integrated Cell-Material Sciences (iCeMS), Kyoto University, Yoshida-Ushinomiya-cho, Sakyo-ku, Kyoto 606-8302, Japan
  • Abstract:We have developed a novel vector constructed with pDNA, polyethylenimine (PEI), and mucin 1 (MUC1) aptamer for tumor-targeted gene delivery. The MUC1 aptamer and non-specific aptamer were employed to coat the pDNA/PEI complexes electrostatically and stable nanoparticles were formed. The addition of a non-specific aptamer to the pDNA/PEI complex decreased gene expression in the human lung cancer cell line, A549 cells expressing MUC1 regularly. At the same time, the pDNA/PEI/MUC1 aptamer complex showed higher gene expression than pDNA/PEI/non-specific aptamer complex. Furthermore, the pDNA/PEI/MUC1 aptamer complex showed markedly high gene expression in tumor-bearing mice; thus, pDNA/PEI/MUC1 aptamer complexes are useful as a tumor-targeted gene delivery system with high transfection efficiency.
    Keywords:pDNA, plasmid DNA   PEI, polyethylenimine   MUC1, mucin 1   polyA, polyadenylic acid   polyIC, polyinosinic-polycytidylic acid   FBS, fetal bovine serum   cDNA, DNA complementary to RNA   BSA, bovine serum albumin   RLU, relative light units
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