Self-assemble gene delivery system for molecular targeting using nucleic acid aptamer

Area of Science:

• Biotechnology
• Nanotechnology
• Molecular Biology

Background:

• Gene therapy holds promise for cancer treatment but requires efficient and targeted delivery vectors.
• Polyethylenimine (PEI) is a common non-viral gene delivery vector, but its tumor-targeting efficiency needs improvement.
• Mucin 1 (MUC1) is overexpressed in various cancers, making it a potential target for tumor-specific therapies.

Purpose of the Study:

• To develop and evaluate a novel tumor-targeted gene delivery vector.
• To investigate the efficacy of MUC1 aptamer-functionalized nanoparticles for gene delivery.
• To assess the gene transfection efficiency of the developed vector in cancer cells and in vivo.

Main Methods:

• A novel vector was constructed using plasmid DNA (pDNA), polyethylenimine (PEI), and a MUC1 aptamer.
• MUC1 aptamer and a non-specific aptamer were used to coat pDNA/PEI complexes, forming stable nanoparticles.
• Gene expression was measured in A549 lung cancer cells and in tumor-bearing mice.

Main Results:

• The pDNA/PEI/MUC1 aptamer complex demonstrated significantly higher gene expression in A549 cells compared to the pDNA/PEI/non-specific aptamer complex.
• The addition of a non-specific aptamer reduced gene expression in MUC1-expressing cancer cells.
• The pDNA/PEI/MUC1 aptamer complex exhibited markedly high gene expression in tumor-bearing mice, indicating effective in vivo tumor targeting.

Conclusions:

• The developed pDNA/PEI/MUC1 aptamer complex serves as an effective tumor-targeted gene delivery system.
• The MUC1 aptamer enhances the specificity and efficiency of gene delivery to tumors.
• This novel vector shows great potential for cancer gene therapy applications with high transfection efficiency.