A DNA Origami-Based Uricase Nanovehicle for Reducing Blood Uric Acid Levels.

Abstract

Exogenous uricase (UOx) has been employed in hyperuricemia treatment, but its foreign protein nature induces an immunogenicity risk and short circulatory half-life <i>in vivo</i>, limiting clinical application. To address these limitations, we developed a DNA origami-based UOx nanovehicle (UOxNV) with a double-layer structure. UOx was site-specifically anchored on a six-helix bundle DNA scaffold, while an albumin-binding domain peptide (ABD) on the outer layer selectively bound serum albumin (SA) to form a protective SA shell. As a proof of concept, we demonstrated UOxNV had enhanced serum stability and a weakened inflammatory response in comparison with those of free UOx. An extended circulatory half-life and a sustained serum uric acid-lowering efficacy were further confirmed in a mouse model. This study presents a novel strategy utilizing DNA nanotechnology to overcome key limitations in current UOx therapeutics, advancing biomedical nanotechnology applications.