Rational design of topology-defined DNA nanoframeworks for antigen delivery and cross-presentation

Area of Science:

• Biotechnology
• Immunology
• Nanotechnology

Background:

• DNA nanoframeworks (DNFs) are programmable platforms for antigen delivery.
• The impact of DNF topology on antigen cross-presentation is not well understood.

Purpose of the Study:

• To investigate how DNF geometry and mechanical properties affect antigen cross-presentation.
• To determine optimal design parameters for DNA-based antigen delivery systems.

Main Methods:

• Systematic comparison of DNFs with varying geometries and mechanical properties.
• Assessment of serum stability, antigen delivery efficiency, cellular uptake, and cross-presentation.
• Evaluation of dendritic cell activation and CD8+ T cell responses.

Main Results:

• Rigid DNFs show enhanced serum stability and antigen delivery efficiency.
• Antigen encapsulation within DNFs promotes cross-presentation compared to surface display.
• Antigen availability, influenced by DNF topology and localization, is key for cross-presentation.

Conclusions:

• Framework topology and antigen localization are critical design parameters for DNFs.
• Antigen delivery efficiency is the primary bottleneck for CD8+ T cell activation via DNFs.