Nanosized, peptide-based multicomponent DNA delivery systems: optimization of endosome escape activity

Area of Science:

• Biotechnology
• Nanotechnology
• Molecular Biology

Background:

• Effective nonviral gene delivery relies on efficient endosome escape.
• Developing safe and effective delivery systems is crucial for gene therapy.

Purpose of the Study:

• To evaluate three endosome-disrupting peptides (HA2(1-20), GALA, KALA) for their efficacy in a multicomponent oligonucleotide delivery system.
• To determine which peptide offers the best balance of endosome escape and toxicity.

Main Methods:

• Multicomponent delivery vectors were synthesized using Copper (I)-catalyzed azide-alkyne cycloaddition.
• Systems were characterized for particle size, DNA condensation, cellular uptake, and endosome escape efficiency.
• Cytotoxicity of each system was assessed.

Main Results:

• All systems successfully condensed plasmid DNA into nanosized particles.
• GALA and KALA containing systems showed the highest cellular uptake and endosome escape.
• KALA incorporation led to increased system toxicity.

Conclusions:

• GALA peptide offers the most promising profile for endosome disruption in nanosized oligonucleotide delivery systems.
• GALA represents a viable candidate for advancing nonviral gene delivery technologies.