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Updated: Mar 26, 2026

Nanosensors to Detect Protease Activity In Vivo for Noninvasive Diagnostics
Published on: July 16, 2018
Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion
Zhao Zhao1,2, Jinglin Fu3, Soma Dhakal4
1Center for Molecular Design and Biomimetics, the Biodesign Institute at Arizona State University, Tempe, Arizona 85287, USA.
Abstract:
Cells routinely compartmentalize enzymes for enhanced efficiency of their metabolic pathways. Here we report a general approach to construct DNA nanocaged enzymes for enhancing catalytic activity and stability. Nanocaged enzymes are realized by self-assembly into DNA nanocages with well-controlled stoichiometry and architecture that enabled a systematic study of the impact of both encapsulation and proximal polyanionic surfaces on a set of common metabolic enzymes. Activity assays at both bulk and single-molecule levels demonstrate increased substrate turnover numbers for DNA nanocage-encapsulated enzymes. Unexpectedly, we observe a significant inverse correlation between the size of a protein and its activity enhancement. This effect is consistent with a model wherein distal polyanionic surfaces of the nanocage enhance the stability of active enzyme conformations through the action of a strongly bound hydration layer. We further show that DNA nanocages protect encapsulated enzymes against proteases, demonstrating their practical utility in functional biomaterials and biotechnology.
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