Diagnostic tests are essential to provide a targeted treatment of infectious diseases and to prevent the further spread of multidrug resistant pathogens. Current methods are either cultivation- or PCR-based and therefore entail significant limitations concerning the clinical need and requirements to characterise pathogens including their resistance mechanisms within 3 hours. In MARA, we aimed to develop and combine three radically novel technologies that should lead to substantial breakthroughs in science, medicine and industry and, as proof-of principle, use them to create a DNA-based molecular toolkit for the characterisation of pathogens.
First, for the detection of pathogen-associated antigens we developed Autonomous Detection Nucleic Acids (AUDENA) that are independent of any laboratory instruments and sophisticated processing. The realisation of the AUDENA concept could lead to an autonomous, stable, simple and very economic novel sensor class applicable for any water-soluble substances. The AUDENAs are superior sensors that can be used for almost all chemical substances and require just a translucent container and a person to identify the colour change. Costs in mass production are below 1€, and thus, AUDENAs could replace current diagnostic and environmental tests.
The second revolutionary technology in MARA employs a novel approach in protein mimicry and creation of artificial enzymes, which represents a breakthrough in several disciplines, such as biotechnology, biomedical manufacturing and the energy sector. A so-called DNA Scaffold Embedded Protein Emulation Complex (D-SEPEC) was created to integrate amino acid-made catalytic centres into supramolecular DNA origami structures and in order to emulate the biological rotary motor of the archaellum and an ion channel using DNA strands.
The third targeted breakthrough in this project was the development of a molecular drill that specifically identifies target cells and destroys them by altering their osmotic system. It was planned to realise this Molecular Robot (MORO) as a DNA nanostructure, driven by an ATP-powered D-SEPEC and aptamers for target recognition. The MORO should lyse the bacterial cells in order to release intracellular antibiotic resistance associated antigens. However, the long-term vision anticipates an application as antibiotic replacement for infectious diseases.
Apart from DNA nanodevice applications in industrial processes, their potential for medical applications such as cancer therapeutics and surgical interventions to counter e.g. artery blockage is tremendous. Being not only highly specific but also biodegradable, the MOROs could have almost unlimited potential in medicine, biotechnology and science. Recent studies have demonstrated the targeted lysis of tumours in mice using DNA nanostructures functionalised with aptamers and proteins.
