Aptamers as a promising approach for the control of parasitic diseases

Abstract

Aptamers are short single-stranded RNA or DNA oligonucleotides that are capable of binding various biological targets with high affinity and specificity. Their identification initially relies on a molecular process named SELEX (Systematic Evolution of Ligands by EXponential enrichment) that has been later modified in order to improve aptamer sensitivity, minimize duration and cost of the assay, as well as increase target types. Several biochemical modifications can help to enhance aptamer stability without affecting significantly target interaction. As a result, aptamers have generated a large interest as promising tools to compete with monoclonal antibodies for detection and inhibition of specific markers of human diseases. One aptamer-based drug is currently authorized and several others are being clinically evaluated. Despite advances in the knowledge of parasite biology and host-parasite interactions from "omics" data, protozoan parasites still affect millions of people around the world and there is an urgent need for drug target discovery and novel therapeutic concepts. In this context, aptamers represent promising tools for pathogen identification and control. Recent studies have reported the identification of "aptasensors" for parasite diagnosis, and "intramers" targeting intracellular proteins. Here we discuss various strategies that have been employed for intracellular expression of aptamers and expansion of their possible application, and propose that they may be suitable for the clinical use of aptamers in parasitic infections.

Several structural motifs cooperate in determining the highly effective anti-thrombin activity of NU172 aptamer

“…NU172 has an IC 50 value of 5–10 μg/ml in plasma in an ecarin clotting time assay obtained by using thromboelastography (23). Currently, NU172 is the only thrombin binding aptamer evaluated in Phase II clinical trials (ClinicalTrials.gov identifier NCT00808964) for anticoagulation in heart disease treatments by ARCA Biopharma, Inc. (3,11,24,25). It induces a short-acting anticoagulation effect and is well tolerated without serious adverse responses (12).…”

Targeting the polyadenylation factor EhCFIm25 with RNA aptamers controls survival in Entamoeba histolytica

“…A large body of biomedical research has shown that aptamers are better than other tools (e.g. antibodies) at detecting and inhibiting target molecules in diagnostics, therapeutics, and drug development 30 . In the present work, we used a systematic evolution of ligands by exponential enrichment (SELEX) protocol to identify RNA aptamers that target the EhCFIm25 protein.…”

Molecular Application of Aptamers in the Diagnosis and Treatment of Cancer and Communicable Diseases

“…Despite the fact that there has been a huge interest in aptamers and that countless scientific studies have been published on the topic, the full potential of aptamers in diagnostics and therapeutics have not yet come to fruition. The approval of Macugen ® (pegatnib sodium) an anti-vascular endothelial growth factor (VEGF) aptamer by the Food and Drug Administration in 2004 [15] for the treatment of age-related macular degeneration is a great milestone and demonstrates the potential of aptamers [14,37,53,128,129]. Since then, many more useful studies have been piloted in the search for solutions for the treatment of HIV, TB, ZIKA, Ebola, cancer, hepatitis and measles.…”

“…Their specificity and affinity-binding properties make them important for use in different applications [11,12]. Although aptamers possess similar binding affinities for their targets as antibodies, varying between nanomolar and picomolar (expressed as dissociation constants, i.e., Kd) [13,14,15], antibodies are still not only immunogenic but is also associated with high production costs. On the other hand aptamers show great supremacy due to their lack of immunogenicity [10,16,17] and synthesis which is done chemically at lower costs, their small sizes makes them versatile and enables them to pass through blood-brain barriers which cannot be achieved with antibodies [18,19].…”