Multivalent cationic dendrofullerenes for gene transfer: synthesis and DNA complexation.

Area of Science:

• Biomaterials Science
• Gene Therapy
• Nanotechnology

Background:

• Gene therapy requires efficient and safe non-viral nucleic acid vectors to overcome biological barriers.
• Current non-viral vectors often face limitations in transfection efficiency and toxicity.
• Developing novel vectors is crucial for advancing clinical gene therapy applications.

Purpose of the Study:

• To synthesize and evaluate novel fullerene-based compounds as non-viral gene delivery vectors.
• To assess the transfection efficiency and cellular toxicity of these fullerene derivatives.
• To investigate the potential of these compounds in forming polyplexes with DNA for gene delivery.

Main Methods:

• Synthesis of hexakis-adducts of [60]fullerene with varying positive ammonium groups (12, 24, 36).
• Synthesis of a tridecafullerene macromolecule with 120 positive charges.
• Transfection of HEK293 cells with a plasmid encoding the green fluorescent protein (EGFP) gene using the synthesized fullerene compounds.
• Evaluation of gene expression and complexation efficiency with DNA.

Main Results:

• Synthesized fullerene derivatives effectively formed polyplexes with DNA.
• Demonstrated successful delivery and expression of the EGFP gene in HEK293 cells.
• Giant tridecafullerene macromolecules exhibited superior DNA complexation and transfection efficiency compared to smaller adducts.

Conclusions:

• Fullerene-based compounds, particularly giant tridecafullerenes, are effective non-viral vectors for gene delivery.
• These novel macromolecules show high transfection efficiency and potential for low toxicity.
• They represent promising candidates for advancing non-viral gene therapy strategies.