Scientists have drawn inspiration from nature to develop a method for detecting DNA.

Roland Krämer and Nora Graf from Ruprecht-Karls University, Heidelberg, Germany, have prepared a reagent that produces an optical response within seconds of coming into contact with DNA. 

The sensing reagent consists of a strand of DNA bound to a metal ion, and an apoenzyme, an enzyme that needs an additional molecule (a cofactor) to work. In this case the cofactor is the metal ion, held away from the enzyme by the DNA strand. When the reagent comes into contact with DNA, the strand of DNA in the reagent releases the metal ion and binds preferentially to the DNA in the sample. The free metal ion then binds to the apoenzyme, activating it. 

Inactive apoenzyme (left) is converted to active holoenzyme (right), indicated by a colour change.

The completed enzyme, carbonic anhydrase, can catalyse reactions that give fluorescence. The researchers found that strands of complimentary DNA are detected quickly, but single-mismatch DNA does not lead to a response. 

'This research is inspired by biological signal cascades, which efficiently enhance molecular signals and rapidly convert them into a biochemical response,' said Krämer. 'Artificial signal cascades hold potential as very simple and sensitive assays for the selective detection of molecular targets, without the need for dedicated instrumentation,' he said.

Sethuraman Mahadevan from Boston University, US, welcomes this work. 'This is a thoughtful model, which integrates basic functionalities like metal chelation, DNA hybridization and metal ion-cofactor dependent enzyme activity, for signaling cascades,' he said.

Currently, the high background activity of the apoenzyme can affect the method's sensitivity, admits Krämer. To counter this, the team is investigating using different enzymes for improved DNA detection.

Rebecca Gillan