Hi-APEX enables spatial molecular mapping without added hydrogen peroxide
Published in Biology, Brain/Neurology, Journals, Tools.
Published October 29, 2026.
A new proximity-labeling method maps molecular neighborhoods without adding hydrogen peroxide. Chen and colleagues introduce Hi-APEX today in Nature Chemical Biology.
Conventional APEX2 labeling requires hydrogen peroxide, which can disturb the redox-sensitive processes researchers want to observe. Hi-APEX instead uses a clickable tetrazine-phenol probe with the existing enzyme. The labeling reaction depends on oxygen and the probe’s tetrazine group, without requiring enzyme engineering.
The researchers benchmarked the method by mapping mitochondrial and secreted molecules. They also examined stress granules and interaction partners of mitochondrial GPX4, identifying the RNA-modifying protein TRMT61B as a promoter of ferroptosis in their experiments.
Importantly, the platform supported protein and RNA proximity labeling in tumor xenografts and hippocampal neurons in vivo, extending the approach beyond cultured cells.
This is a research tool for studying spatial biology, stress responses and cell-death pathways. Its reported compatibility under the tested conditions does not establish universal suitability across tissues or a therapeutic effect.
Source: Chen et al., Nature Chemical Biology. Published October 29, 2026. DOI: 10.1038/s41589-026-02356-1.