Molecular Dx Significance 5/10

Fusion LAMP combined with CRISPR/Cas13a enables dual-target MRSA detection

Investigators developed a novel isothermal amplification technique, fusion LAMP, that joins two independent DNA fragments in a single reaction. When coupled with CRISPR/Cas13a to form an AND-gate platform (FLCC), the assay generates fluorescence only when two target sequences are present simultaneously. In proof-of-concept testing for methicillin-resistant Staphylococcus aureus (MRSA), the method achieved a limit of detection of 10 copies/μL, showed no cross-reactivity with related strains, and correctly identified 19 clinical isolates. The dual-target design reduces false positives and offers a streamlined approach for multiplex nucleic acid detection, with potential utility for decentralized pathogen screening given the isothermal nature of LAMP.

The original study

LAMP-Based Two-DNA-Fragment Fusion and Its Application in Nucleic Acid Detection.

Authors
Zhou Q, Xu B, Wang Y, Yang X, Wang L, Zheng X, et al.
Journal
ACS synthetic biology
Type
Journal Article
PMID
42435429
Read the original study →

Original abstract

Loop-mediated isothermal amplification (LAMP) continuously generates strand-displaced single-stranded DNA intermediates, providing the possibility of assembling DNA fragments. Here, we developed a novel two-DNA-fragment fusion technique, termed fusion LAMP, which is an isothermal DNA-fusion strategy that enables the fusion of two independent DNA fragments within a single amplification reaction. By combining fusion LAMP with CRISPR/Cas13a, we further established an "AND-gate" nucleic acid detection platform, termed Fusion LAMP-Coupled CRISPR/Cas13a (FLCC), which enables concurrent detection of two targets by reading the fusion product-triggered fluorescence signals. This platform generates signals only when two targets are present simultaneously. To prove this concept, we then employed FLCC to identify the methicillin-resistant Staphylococcus aureus (MRSA). This method achieved a limit of detection of 10 copies/μL of MRSA genomic DNA and showed no cross-reactivity with closely related bacterial strains. Furthermore, we validated its feasibility by detecting 19 clinical isolates, demonstrating a simple and accurate approach for MRSA detection. Collectively, the FLCC platform ensures identifying pathogens accurately and provides a promising diagnostic approach for detecting complex genetic targets.