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Programmable pH-responsive DNA inter-strand matching (PRISM) for precision molecular band-pass actuation.

Xiaole Han^1,2, Hongyan Yu², Xiaomei Lin²

¹Department of Neurosurgery, Laboratory of Neurological Diseases and Interdisciplinary Medicine, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Chongqing, 400016, China.

|June 29, 2026

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Researchers developed a DNA-based system called PRISM that acts as a molecular band-pass filter. This novel pH-sensing technology precisely distinguishes subtle pH differences in biological environments, enabling advanced diagnostics and therapeutics.

Area of Science:

Molecular Biology
Biotechnology
Chemical Biology

Background:

Precise sensing of physiological pH is crucial for molecular regulation in biological systems.
Traditional pH-responsive systems struggle to differentiate subtle pH variations, such as those in tumor microenvironments (pH 6.5-6.8).

Purpose of the Study:

To develop a novel pH-sensing strategy for precise molecular regulation.
To create a system capable of distinguishing narrow physiological pH ranges for improved diagnostics.

Main Methods:

Developed PRISM (pH-Responsive DNA Inter-Strand Matching), a DNA-based molecular band-pass filter.
Integrated low-pH OFF (i-motif) and high-pH OFF (C-A mismatch) modules for non-monotonic actuation.
Utilized sequence-level thermodynamic design to define a controllable operational window.

Keywords:

CRISPR/Cas13a DNA nanotechnology band-pass filter pH-responsive tumor microenvironment

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Main Results:

PRISM demonstrated tunable band-pass signal responses, enabling precise pH sensing.
Successfully applied PRISM for high-contrast imaging of pH gradients on HeLa cell surfaces.
Showcased PRISM's ability to regulate DNA aptamers and control CRISPR/Cas13a activity based on pH.

Conclusions:

PRISM offers a modular, biocompatible strategy for precise windowed pH regulation, moving beyond conventional monotonic switching.
The platform facilitates high-fidelity diagnostic imaging and localized therapeutic activation in subtle pathological microenvironments.
PRISM enables the development of intelligent theranostic platforms without complex bioconjugation.