DNA aptamers for the recognition of HMGB1 from Plasmodium falciparum

Joseph, Diego F.; Nakamoto, Jose A.; Ruiz, Oscar Andree Garcia; Peñaranda, Katherin; Sanchez-Castro, Ana Elena; Castillo, Pablo Soriano; Milón, Pohl

doi:10.1371/journal.pone.0211756

Cited by 17 publications

(13 citation statements)

References 63 publications

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“…There is a critical need for a better understanding of malaria as well as tests for the rapid diagnosis and surveillance of malaria. As such, there have been many reports describing the selection of new aptamers 3,4,11,[58][59][60][61] to malaria targets as well as novel aptamer-based biosensors [62][63][64] . Previous studies generating aptamer probes to the IE surface have used pre-defined Plasmodium recombinant protein fragments or intact IEs and sophisticated microfluidic fabrication.…”

Section: Discussionmentioning

confidence: 99%

High-efficiency enrichment enables identification of aptamers to circulating Plasmodium falciparum-infected erythrocytes

Oteng

McKeague

2020

Sci Rep

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Plasmodium falciparum is the causative agent of the deadliest human malaria. New molecules are needed that can specifically bind to erythrocytes that are infected with P. falciparum for diagnostic purposes, to disrupt host-parasite interactions, or to deliver chemotherapeutics. Aptamer technology has the potential to revolutionize biological diagnostics and therapeutics; however, broad adoption is hindered by the high failure rate of the systematic evolution of ligands by exponential enrichment (SELEX). Here we performed parallel SELEX experiments to compare the impact of two different methods for single-strand recovery on the efficiency of aptamer enrichment. Our experimental results and analysis of SELEX publications spanning 13 years implicate the alkaline denaturation step as a significant cause for inefficient aptamer selection. Thus, we applied an exonuclease single-strand recovery step in our SELEX to direct aptamers to the surface of erythrocytes infected with P. falciparum. The selected aptamers bind with high affinity (low nanomolar K d values) and selectivity to exposed surface proteins of both laboratory parasite strains as well isolates from patients in Asia and Africa with clinical malaria. The results obtained in this study potentially open new approaches to malaria diagnosis and surveillance. Malaria is a global health problem, with 228 million clinical episodes and an estimated 405,000 deaths each year 1. Plasmodium falciparum is the causative agent of the deadliest human malaria. A constellation of parasite-encoded proteins is displayed on the surface of infected erythrocytes (IEs) that are important in the life cycle of the parasite and mediate critical host-parasite interactions. One important host-parasite interaction is IE sequestration in the microvasculature which is thought to lead to the most severe manifestations of the disease. Therefore, ligand-binding molecules that can specifically identify and bind to IEs may disrupt important host-parasite interactions, deliver chemotherapeutics to parasitized cells, and have potential to further our understanding of the diversity of proteins expressed on the IE surface 2-5. Indeed, antibodies targeting IEs disrupt pathogenesis and contribute to naturally-acquired immunity to malaria 6-9. Aptamers are an alternative to antibodies that may sufficiently serve as molecular recognition agents of IEs. Several aptamers have been selected that bind to targets and biomarkers of malaria infection (see review 10 for examples). Aptamers are single-stranded nucleic acids that bind target molecules with antibody-like affinity and specificity through shape complementarity 11,12. However, the nucleic acid composition of aptamers presents several advantages over antibodies including increased stability, cell-free synthesis (either by PCR or chemical synthesis), and simple modification for detection and immobilization. Aptamers have been developed against small molecules, peptides, proteins, and whole cells including bacteria and parasites 3,13-16. As such, aptame...

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Section: Discussionmentioning

confidence: 99%

High-efficiency enrichment enables identification of aptamers to circulating Plasmodium falciparum-infected erythrocytes

Oteng

McKeague

2020

Sci Rep

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“…To validate the molecular binding affinity of the candidate sequences and protein, we used ZDOCK, which is a computational simulation tool for measuring molecular interactions (note that the docking simulation was not used in the generation of candidate sequences in Apta-MCTS). ZDOCK is commonly used in many molecular interaction studies, such as the theoretical molecular interactions between aptamers and HMG-box Pf [ 37 ].…”

Section: Methodsmentioning

confidence: 99%

Predicting aptamer sequences that interact with target proteins using an aptamer-protein interaction classifier and a Monte Carlo tree search approach

Lee

Jang²,

Kang³

et al. 2021

PLoS ONE

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Oligonucleotide-based aptamers, which have a three-dimensional structure with a single-stranded fragment, feature various characteristics with respect to size, toxicity, and permeability. Accordingly, aptamers are advantageous in terms of diagnosis and treatment and are materials that can be produced through relatively simple experiments. Systematic evolution of ligands by exponential enrichment (SELEX) is one of the most widely used experimental methods for generating aptamers; however, it is highly expensive and time-consuming. To reduce the related costs, recent studies have used in silico approaches, such as aptamer-protein interaction (API) classifiers that use sequence patterns to determine the binding affinity between RNA aptamers and proteins. Some of these methods generate candidate RNA aptamer sequences that bind to a target protein, but they are limited to producing candidates of a specific size. In this study, we present a machine learning approach for selecting candidate sequences of various sizes that have a high binding affinity for a specific sequence of a target protein. We applied the Monte Carlo tree search (MCTS) algorithm for generating the candidate sequences using a score function based on an API classifier. The tree structure that we designed with MCTS enables nucleotide sequence sampling, and the obtained sequences are potential aptamer candidates. We performed a quality assessment using the scores of docking simulations. Our validation datasets revealed that our model showed similar or better docking scores in ZDOCK docking simulations than the known aptamers. We expect that our method, which is size-independent and easy to use, can provide insights into searching for an appropriate aptamer sequence for a target protein during the simulation step of SELEX.

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“…To detect PfGDH in serum samples, they 1) coupled this aptamer with carbon dots as the probe 219 , 2) coupled the aptamer with dye as the catcher for an enzyme-catalyzed reaction 220 , and 3) applied this aptamer as the capture in a field-effect transistor biosensor 221 , resulting in detection limits of 2.85 nM, 63.97 pM, and 48.6 pM, respectively. For rapid diagnostic tests for Plasmodium infection, Joseph et al identified high mobility group box 1 protein (HMGB1) as a biomarker for Plasmodium infection using gene expression databases, ribosome profiling analysis, and structural modeling 222 . Later, they immobilized biotinylated HMG-box onto streptavidin-coated magnetic beads for protein-SELEX and developed several DNA aptamers of potential use for malaria diagnosis.…”

Section: Potential Utility Of Aptamer Technology For Pathogen Detectionmentioning

confidence: 99%

Oligonucleotide aptamers for pathogen detection and infectious disease control

Wan

Liu

2021

Theranostics

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During an epidemic or pandemic, the primary task is to rapidly develop precise diagnostic approaches and effective therapeutics. Oligonucleotide aptamer-based pathogen detection assays and control therapeutics are promising, as aptamers that specifically recognize and block pathogens can be quickly developed and produced through simple chemical synthesis. This work reviews common aptamer-based diagnostic techniques for communicable diseases and summarizes currently available aptamers that target various pathogens, including the SARS-CoV-2 virus. Moreover, this review discusses how oligonucleotide aptamers might be leveraged to control pathogen propagation and improve host immune system responses. This review offers a comprehensive data source to the further develop aptamer-based diagnostics and therapeutics specific for infectious diseases.

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DNA aptamers for the recognition of HMGB1 from Plasmodium falciparum

Cited by 17 publications

References 63 publications

High-efficiency enrichment enables identification of aptamers to circulating Plasmodium falciparum-infected erythrocytes

High-efficiency enrichment enables identification of aptamers to circulating Plasmodium falciparum-infected erythrocytes

Predicting aptamer sequences that interact with target proteins using an aptamer-protein interaction classifier and a Monte Carlo tree search approach

Oligonucleotide aptamers for pathogen detection and infectious disease control

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