Controlling intracellular processing to enhance spherical nucleic acid immune stimulation.

ABSTRACT: To mount a robust and durable immune response, the antigen in a vaccine must be processed efficiently in the appropriate intracellular compartment. Here, we report an approach for optimizing the antigen processing pathway and efficiency by using the modular design of spherical nucleic acid (SNA) nanostructures. We utilized the substrate specificity of endoplasmic reticulum aminopeptidase1 (ERAP1), a protease known to generate major histocompatibility complex class I (MHC I) epitopes in the endoplasmic reticulum, to design two ERAP1-responsive peptide linkers (EPLs). The peptide linkers append the peptide antigen onto the SNAs to bias the processing pathway toward ERAP1 and to vary the antigen processing efficiency. The two EPLs varied ERAP1 antigen processing efficiency by 10-fold. Subsequ

SUBMITTER: Kang J 

PROVIDER: S-EPMC12625926 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature