%0 Journal Article
%T Enhancing CRISPR/Cas-mediated electrochemical detection of nucleic acid using nanoparticle-labeled covalent organic frameworks reporters.
%A Qian H
%A Guo X
%A Yang H
%A Bao T
%A Wu Z
%A Wen W
%A Zhang X
%A Wang S
%J Biosens Bioelectron
%V 261
%N 0
%D 2024 Oct 1
%M 38924815
%F 12.545
%R 10.1016/j.bios.2024.116522
%X Molecular detection of nucleic acid plays an important role in early diagnosis and therapy of disease. Herein, a novel and enhanced electrochemical biosensor was exploited based on target-activated CRISPR/Cas12a system coupling with nanoparticle-labeled covalent organic frameworks (COFs) as signal reporters. Hollow spherical COFs (HCOFs) not only served as the nanocarriers of silver nanoparticles (AgNPs)-DNA conjugates for enhanced signal output but also acted as three-dimensional tracks of CRISPR/Cas12a system to improve the cleavage accessibility and efficiency. The presence of target DNA triggered the trans-cleavage activity of the CRISPR/Cas12a system, which rapidly cleaved the AgNPs-DNA conjugates on HCOFs, resulting in a remarkable decrease of the electrochemical signal. As a proof of concept, the fabricated biosensing platform realized highly sensitive and selective detection of human papillomavirus type 16 (HPV-16) DNA ranging from 100 fM to 1 nM with the detection limit of 57.2 fM. Furthermore, the proposed strategy provided a versatile and high-performance biosensor for the detection of different targets by simple modification of the crRNA protospacer, holding promising applications in disease diagnosis.