New Method for Labeling DNA Bases for Sequencing Developed

A newly developed method for labeling DNA could help simplify and accelerate sequencing, according to a recently published paper in the Journal of the American Chemical Society.

This new approach uses electrochemical detection and redox labels. The team, headed by Michael Hocek of IOCB Prague, designed and synthesized artificial nucleotides with redox labels that can be oxidized on a gold or carbon electrode at a specific potential to produce a measurable and analytically useful signal. These labels are carboranes, cage structures composed of boron and carbon atoms, into which other metal atoms can be incorporated.

The modified nucleotides have been engineered so that the DNA polymerase can incorporate them into a newly synthesized DNA strand. As a result, the researchers were able to prepare a strand of DNA comprising modified nucleotides. At the same time, each of the four types of nucleotide carries its own unique label allowing for its subsequent identification.

According to the team, until now, researchers had only managed to label and measure one, at most two, types of redox-labeled nucleotides in a single strand of DNA. With their new approach, because each of the modified nucleotides carries its own label that during electrochemical detection gives a specific oxidation signal at varying potentials, the individual types of nucleotides can be distinguished. Moreover, the size of each signal is dependent on the number of copies of the given nucleotide in the DNA, which then makes it possible to quickly determine the relative representation of individual nucleotides in the measured DNA.

The newly developed electrochemical coding of DNA bases offers a range of advantages, such as simpler and more affordable instrumentation and faster analysis. The method also reportedly holds promise for DNA sequencing and diagnostic applications as well as for development of new DNA chips.