Self-feedback cascading DNA circuit encapsulated within a gene-modified bifunctional virus-inspired nanovector for...

Despite being viewed as a potent analytical methodology for imaging disease biomarkers in live organisms, DNA circuit-dependent biosensors are impeded by inadequate detection sensitivity, unsatisfactory bio-uptake efficiency, and measurement inaccuracies. In an endeavor to overcome these challenges, we herein introduce several effective resolutions.

First, a hybridization chain reaction is combined with catalytic hairpin assembly to carry out a self-feedback cascading mechanism, offering two rounds of signal amplification to enhance biosensing performance. After that, nucleic acid modules are encapsulated within a gene-modified virus-inspired nanovector equipped with both bio-targeting and cytomembrane-penetrating functions, significantly improving the biosensor's uptake by biological media. Additionally, a photocleavage-linker is inserted into this assay system to facilitate a light-gated spatiotemporal pattern, preventing the biosensor from remaining in an always-active status throughout bio-delivery to promote imaging accuracy. For the intent of conceptual demonstration, our DNA circuit permits ultra-sensitive and specific detection of microRNA-21, a potential biomarker for a range of cancers, in solution analysis. Of greater importance, we present a biosensing toolbox that has impressive imaging capabilities for measuring low-abundance analytes in live cell lines as well as animal models.

This work makes a meaningful contribution to the progress of DNA circuits for use in disease diagnostics.