Multivalent Aptamer Approach: Designs, Strategies, and Applications

Abstract

Aptamers are short and single-stranded DNA or RNA molecules with highly programmable structures that give them the ability to interact specifically with a large variety of targets, including proteins, cells, and small molecules. Multivalent aptamers refer to molecular constructs that combine two or more identical or different types of aptamers. Multivalency increases the avidity of aptamers, a particularly advantageous feature that allows for significantly increased binding affinities in comparison with aptamer monomers. Another advantage of multivalency is increased aptamer stabilities that confer improved performances under physiological conditions for various applications in clinical settings. The current study aims to review the most recent developments in multivalent aptamer research. The review will first discuss structures of multivalent aptamers. This is followed by detailed discussions on design strategies of multivalent aptamer approaches. Finally, recent developments of the multivalent aptamer approach in biosensing and biomedical applications are highlighted.

Electrical biosensing system utilizing ion-producing enzymes conjugated with aptamers for the sensing of severe acute respiratory syndrome coronavirus 2

“…The limit of detection was 100 copies/μL when the RBD-1C aptamer-ALP conjugates were used, which was 10 times lower than that when the antibody-ALP conjugates were examined. Due to the tetrameric nature of streptavidin and the smaller size of the aptamers compared with antibodies, the conjugated aptamers with streptavidin-coupled ALPs may confer architectural multivalency to the aptamers, which potently increases their avidity and elevates binding to the densely positioned S proteins on the surface of SARS-CoV-2 [ 44 ]. Therefore, aptamers may be more advantageous than conventional antibodies for detecting the S proteins of intact SARS-CoV-2.…”

“…In this proof-of-concept study, the proposed detection technology was developed using a novel combination of aptamer recognition moieties, ion-producing enzymes, and electrical sensing platforms. Compared to antibodies, small aptamers are highly avid when conjugated with scaffolds such as multimer-forming streptavidin or enzymes, rendering them particularly applicable to detecting densely assembled targets, including membrane-bound targets and cellular or viral capsid proteins [ 44 ]. An important limitation of this method is that it requires the use of costly pH meters, which are not suitable for extensive clinical trials.…”

Aptamer-based technology for gastric cancer theranostics

“…Aptamers are single-stranded nucleic acids chosen through the systematic evolution of ligands by exponential enrichment (SELEX) screening. 11,12 Aptamer discovery methods have been constantly improved over the years. Aptamers show high affinity and specicity for broad classes of targets, beneting from their topological secondary and tertiary structures under certain conditions.…”

Ultrasensitive thrombin sensing platform based on three-way junction initiated dual signal amplification

“…However, the immunoassay is often criticized for relatively poor sensitivity, high labor intensity and narrow detection range. Aptamers, as small oligonucleotides that can specifically recognize and bind with biomolecules, are widely exploited to construct aptasensors (Wang et al 2022;Zhang et al 2022a). Aptasensor can be used in a variety of experimental and clinical settings, including the identification of diseases and the delivery of medications, due to its advantages of low cost, ease of modification, and quick response (Zhao et al 2020a, b).…”