Aptamers Selected for Recognizing Amyloid β-Protein—A Case for Cautious Optimism

Abstract

Aptamers are versatile oligonucleotide ligands used for molecular recognition of diverse targets. However, application of aptamers to the field of amyloid β-protein (Aβ) has been limited so far. Aβ is an intrinsically disordered protein that exists in a dynamic conformational equilibrium, presenting time-dependent ensembles of short-lived, metastable structures and assemblies that have been generally difficult to isolate and characterize. Moreover, despite understanding of potential physiological roles of Aβ, this peptide has been linked to the pathogenesis of Alzheimer disease, and its pathogenic roles remain controversial. Accumulated scientific evidence thus far highlights undesirable or nonspecific interactions between selected aptamers and different Aβ assemblies likely due to the metastable nature of Aβ or inherent affinity of RNA oligonucleotides to β-sheet-rich fibrillar structures of amyloidogenic proteins. Accordingly, lessons drawn from Aβ–aptamer studies emphasize that purity and uniformity of the protein target and rigorous characterization of aptamers’ specificity are important for realizing and garnering the full potential of aptamers selected for recognizing Aβ or other intrinsically disordered proteins. This review summarizes studies of aptamers selected for recognizing different Aβ assemblies and highlights controversies, difficulties, and limitations of such studies.

Selection of Membrane RNA Aptamers to Amyloid Beta Peptide: Implications for Exosome-Based Antioxidant Strategies

“…Aptamers selected to Aβ40 conjugated to gold nanoparticles are the only ones displaying a binding affinity to an oligomeric model of non-membrane Aβ40 with very low affinity [19]. However, the reported K D values remain questionable, and they were not tested for their cross-reactivity with fibrillary assemblies of Aβ or of other amyloidogenic proteins [20].…”

Fluorescent aptamers for detection and treatment of pathogenic bacteria and cancer

“…With the increased popularity and utilization of biologicals as instruments for diagnosis and therapy, the shortcomings associated with monoclonal antibodies have also become more apparent. Although the core process of aptamer creation and selection was established in 1990, it took nearly two decades before studies to develop improved SELEX iterations or research to prove superiority to mAbs gained impetus (Rahimi, 2018). Inaccessibility to the SELEX technology due to patent rights, familiarity and widespread use of mAb production technology, burgeoning market for antibodies in disease detection and treatment were some of the reasons that diverted attention from aptamer research and development (Nimjee, Rusconi, & Sullenger, 2005; "Global Monoclonal Antibodies," 2018; Grilo & Mantalaris, 2019;Marks, 2012;Wade, 1980;Baird, 2010).…”

(Bio)chemical Strategies To Modulate Amyloid-β Self-Assembly

“…A potential drawback to the use of antibodies is their large size; although the use of antibody fragments or of camel single domain antibodies might be very promising 73 . In addition, aptamers, oligonucleotide ligands with high affinity and specificity, have also been developed toward Aβ binding 74 .…”