Aptamer-mediated Plasmodium-specific diagnosis of malaria

Cheung, Yiu-ming; Dirkzwager, Roderick M.; Wong, Weng-Fai; Cardoso, Josiane; Costa, Joana D'Arc Neves; Tanner, Julian A.

doi:10.1016/j.biochi.2017.10.017

Cited by 49 publications

(54 citation statements)

References 34 publications

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“…Such versatility arises from uncountable chemical modifications that are commercially available. Aptamer-tethered enzymes have been shown of great sensibility and to differentiate P. falciparum from P. vivax in blood samples [53]. Additionally, the development of aptamers using species specific epitopes allowed to isolate an aptamer that could accurately discriminate between the above species [47].…”

Section: Discussionmentioning

confidence: 99%

DNA aptamers for the recognition of HMGB1 from Plasmodium falciparum

Joseph

Nakamoto

Ruiz

et al. 2019

Preprint

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21 Rapid Diagnostic Tests (RDTs) for malaria are restricted to a few biomarkers and antibody-22 mediated detection. However, the expression of commonly used biomarkers varies 23 geographically and the sensibility of immunodetection can be affected by batch-to-batch 24 differences or limited thermal stability. In this study we aimed to overcome these limitations 25 by identifying a potential biomarker and by developing molecular sensors based on aptamer 26 technology. Using gene expression databases, ribosome profiling analysis, and structural 27 modeling, we find that the High Mobility Group Box 1 protein (HMGB1) of Plasmodium 28 falciparum is highly expressed, structurally stable and steadily present along all blood-stages 29 of P. falciparum infection. To develop biosensors, we used in vitro evolution techniques to 30 produce DNA aptamers for the recombinantly expressed HMG-box, the conserved domain 31 of HMGB1. An evolutionary approach for evaluating the dynamics of aptamer populations 32 suggested three predominant aptamer motifs. Representatives of the aptamer families were 33 tested for binding parameters to the HMG-box domain using microscale thermophoresis and 34 rapid kinetics. Dissociation constants of the aptamers varied over two orders of magnitude 35 between nano-and micromolar ranges while the aptamer-HMG-box interaction occurred in 36 less than 30 seconds. The specificity of aptamer binding to the HMG-box of P. falciparum 37 compared to its human homolog depended on pH conditions. Altogether, our study proposes 38 HMGB1 as a potential biomarker and a set of sensing aptamers that can be further developed 39 into rapid diagnostic tests for P. falciparum detection. 40 41 42 3 43 44 45 46 47 Malaria is an infectious disease that affects animals and humans, caused by protozoans of the 48 genus Plasmodium. Malaria remains the cause of 435,000 deaths worldwide, with 219 49 million cases reported during 2017 [1]. Accurate treatment requires the identification of the 50 parasite of the genus Plasmodium, in addition to the species causing the disease. Currently, 51 there are several methods to diagnose malaria, such as PCR-based, Giemsa microscopy, and 52 Rapid Diagnostic Tests (RDTs). Among these options, the last two appear to be suitable for 53 low-income and mostly affected countries; nonetheless, they also present certain limitations 54 [2]. 55 Giemsa microscopy is inexpensive to perform, can differentiate malaria species and stages, 56 and can quantify the parasites [2]. However, well-trained personnel is required and, 57 frequently unavailable in low-income countries [2]. RDTs, on the other hand, 58 detect Plasmodium spp. biomarker antigens in a small amount of blood using immobilized 59 antibodies. The two most used biomarkers are histidine-rich protein 2 (HRP-2) and lactate 60 dehydrogenase (LDH), which have been shown of high sensitivity and specificity for 61 detecting P. falciparum [3]. However, P. falciparum strains lacking the HRP-2 and HRP-3 62 genes have appeared, increasing false negative re...

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Section: Discussionmentioning

confidence: 99%

DNA aptamers for the recognition of HMGB1 from Plasmodium falciparum

Joseph

Nakamoto

Ruiz

et al. 2019

Preprint

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“…Label‐free detection is another aspect of aptamer‐based microfluidic detection (Figure c). A Plasmodium falciparum lactate dehydrogenase (PfLDH) specific aptamer was identified by our team (Tanner's research group) and an aptamer‐tethered enzyme capture (APTEC) assay which bases detection on the intrinsic enzyme activity of the captured PfLDH malaria biomarker protein was developed . It has since been incorporated to a range different detection formats 9d,e,82.…”

Section: Microfluidic Selection Of Aptamersmentioning

confidence: 99%

Microfluidic Technology for Nucleic Acid Aptamer Evolution and Application

et al. 2019

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The intersection of microfluidics and aptamer technologies holds particular promise for rapid progress in a plethora of applications across biomedical science and other areas. Here, the influence of microfluidics on the field of aptamers, from traditional capillary electrophoresis approaches through innovative modern‐day approaches using micromagnetic beads and emulsion droplets, is reviewed. Miniaturizing aptamer‐based bioassays through microfluidics has the potential to transform diagnostics and embedded biosensing in the coming years.

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“…P. falciparum has various biomarkers including lactate dehydrogenase (LDH), histidine rich protein2 (HRP2), aldolase, and hypoxanthine phosphoribosyl transferase [5]. Conventional diagnosis of P. falciparum is mainly dependent on HRP2 detection by immunoassay [6]. However, HRP2 deletion mutants have been reported in several countries [7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Simple, rapid, and accurate malaria diagnostic platform using microfluidic-based immunoassay of Plasmodium falciparum lactate dehydrogenase

et al. 2020

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This work reports on a rapid diagnostic platform for the detection of Plasmodium falciparum lactate dehydrogenase (PfLDH), a representative malaria biomarker, using a microfluidic microplate-based immunoassay. In this study, the microfluidic microplate made it possible to diagnose PfLDH with a small volume of sample (only 5 μL) and short time (< 90 min) compared to conventional immunoassays such as enzyme-linked immunosorbent assay (ELISA). Moreover, the diagnostic performance of PfLDH showed high sensitivity, specificity, and selectivity (i.e., 0.025 pg/μL in phosphate-buffered saline and 1 pg/μL in human serum). The microfluidic-based microplate sensing platform has the potential to adapt simple, rapid, and accurate diagnoses to the practical detection of malaria.

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Aptamer-mediated Plasmodium-specific diagnosis of malaria

Cited by 49 publications

References 34 publications

DNA aptamers for the recognition of HMGB1 from Plasmodium falciparum

DNA aptamers for the recognition of HMGB1 from Plasmodium falciparum

Microfluidic Technology for Nucleic Acid Aptamer Evolution and Application

Simple, rapid, and accurate malaria diagnostic platform using microfluidic-based immunoassay of Plasmodium falciparum lactate dehydrogenase

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