Nucleic acids aptamers for malaria diagnosis - discovery, structure and application

Abstract

Better malaria diagnosis approaches at the point of care are critically needed. Antibody-based rapid diagnostic tests have made a major positive impact on malaria management. However, cost, robustness, and challenges in manufacturing remain as issues innate to antibodies in tests suitable for widespread use in the developing world. We have been researching DNA aptamers against malaria diagnostic proteins that may underpin a change in the underlying molecular recognition technology for malaria diagnostic tests. Highly specific and tight-binding aptamers against a diagnostic protein target for pan-species malaria detection (lactate dehydrogenase) and a Plasmodium falciparum specific target (histidine rich protein II) were identified. We solved the X-ray crystal structure of a DNA aptamer in complex with its lactate dehydrogenase target, which elucidated the mechanism of discriminatory binding to Plasmodium over human lactate hydrogenase which we had optimized using counter selection techniques. We conjugated the aptamers to nanoparticles and have developed a colorimetric biosensor for the diagnostic targets. Research is ongoing based on this new technology to develop a diagnostic device suitable for clinical trials that we aim to be more sensitive, less expensive, more robust and easier to manufacture than the best antibody-based rapid diagnostic tests for malaria available today.