Detecting infectious and autoimmune antibodies with a DNA nanomachine

Aims to replace the current slow, cumbersome, expensive diagnostic process
October 7, 2015

A nanoscale DNA “machine,” shown in this illustration bound to an antibody (yellow), rapidly lights up when it recognizes specific target antibodies (credit: Marco Tripodi)

An international team of scientists has developed a nanomachine using synthetic DNA for rapid, sensitive, low-cost diagnosis of infectious and auto-immune diseases, including HIV, at the point of care. It aims to replace the current slow, cumbersome, and expensive current process of detecting the protein antibodies used for diagnosis.

An antibody causes a structural change (or switch) in the device, which generates a light signal. The sensor does not need to be chemically activated and is rapid — acting within five minutes — enabling the targeted antibodies to be easily detected, even in complex clinical samples such as blood serum.

The antibody-targeting sensor is composed of a light-emitting fluorophore (F) and quencher (green circle) connected to two single-stranded DNA tails joined to the appropriate recognition element (red hexagons) for a given test. When a target antibody is detected by the two recognition elements, they open the stem, activating the fluorophore. (credit: S. Ranallo et al./Angew. Chem. Int. Ed.)

The research is described in the October issue of the journal Angewandte Chemie.

“One of the advantages of our approach is that it is highly versatile,” said Prof. Francesco Ricci, of the University of Rome, Tor Vergata, senior co-author of the study. “This DNA nanomachine can be in fact custom-modified so that it can detect a huge range of antibodies; this makes our platform adaptable for many different diseases.”

“Our modular platform provides significant advantages over existing methods for the detection of antibodies,” added Prof. Vallée-Bélisle of the University of Montreal, the other senior co-author of the paper. “It is rapid, does not require reagent chemicals, and may prove to be useful in a range of different applications such as point-of-care diagnostics and bioimaging.”

The researchers plan to allow the light-emitting signal to be detected by a mobile phone.

A University of California, Santa Barbara scientist was also involved in the research.

Abstract of A Modular, DNA-Based Beacon for Single-Step Fluorescence Detection of Antibodies and Other Proteins

A versatile platform for the one-step fluorescence detection of both monovalent and multivalent proteins has been developed. This system is based on a conformation-switching stem–loop DNA scaffold that presents a small-molecule, polypeptide, or nucleic-acid recognition element on each of its two stem strands. The steric strain associated with the binding of one (multivalent) or two (monovalent) target molecules to these elements opens the stem, enhancing the emission of an attached fluorophore/quencher pair. The sensors respond rapidly (<10 min) and selectively, enabling the facile detection of specific proteins even in complex samples, such as blood serum. The versatility of the platform was demonstrated by detecting five bivalent proteins (four antibodies and the chemokine platelet-derived growth factor) and two monovalent proteins (a Fab fragment and the transcription factor TBP) with low nanomolar detection limits and no detectable cross-reactivity.