Image: By attaching specific aptamer molecules to a DNA backbone, researchers have made it easier to detect rare molecules associated with early disease (Photo courtesy of Dr. Joshua Edel, Imperial College London).
A novel, highly sensitive blood test for a wide range of serum proteins combines aptamer-DNA capture molecules with nanopore-based single molecule sensing.
Nucleic acid aptamers are nucleic acid species that have been engineered through repeated rounds of in vitro selection to bind to various molecular targets such as small molecules, proteins, nucleic acids, and even cells, tissues, and organisms. Aptamers are useful in biotechnological and therapeutic applications as they offer molecular recognition properties that rival that of antibodies. In addition to their discriminate recognition, aptamers offer advantages over antibodies as they can be engineered completely in a test tube, are readily produced by chemical synthesis, possess desirable storage properties, and elicit little or no immunogenicity in therapeutic applications. Relative to monoclonal antibodies, DNA aptamers are small, stable, and non-immunogenic.
Investigators at Imperial College London (United Kingdom) recently described a fully flexible, scalable, and low-cost detection platform to sense multiple protein targets simultaneously by grafting specific aptamer sequences along the backbone of a double-stranded DNA carrier.
Protein bound to the aptamer produced unique ionic current signatures, which facilitated accurate target recognition. This powerful approach enabled the investigators to differentiate individual protein sizes via characteristic changes in the sub-peak current. By using DNA carriers it was possible to perform single-molecule screening in human serum at ultra-low protein concentrations.
The investigators pointed out that the system could be expanded to more than five different aptamers, allowing simultaneous detection of multiple biomarkers. Furthermore, since the biomarkers were detected in human serum, preparation time was minimized and was less costly than traditional tests to detect these proteins.
Contributing author Dr. Alex Ivanov, research fellow in the department of chemistry at Imperial College London, said, "The detection of single molecules of biomarkers represents the ultimate in sensitivity for early diagnosis. We have now shown that this is possible to perform such measurements in real human samples, opening up the potential for meaningful early diagnosis."
The aptamer-based nanopore analytical method was described in the November 16, 2017, online edition of the journal Nature Communications.
Imperial College London