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.
Highlights
IntroductionThe concept of multivalency is intrinsic to nature. For instance, marine mussels use multiple byssal threads to ensure attachment to rock surfaces, and octopus appendages make use of numerous suckers to efficiently capture preys
Higher local aptamer concentration leads to a higher chance of interacrapidly degraded by nuclease, a major drawback limiting their in vivo applications tion between aptamers and cell-surface ligands
After the initial binding of an studies have demonstrated that conjugating multiple aptamers onto nanoparaptamer with its ligand, nearby aptamers can be readily recruited to facilitate additional ticles canthereby successfully provide resistance enzymatic degradation and increase binding, leading to a higher avidity.toPhysiological conditions present another nucleic challenge for aptamers; in their monomeric aptamers have shown to of be the rapidly acid stabilities due to increased local saltform, concentrations onbeen the surfaces nanopartidegraded by nuclease, a major drawback limiting their in vivo applications
Summary
The concept of multivalency is intrinsic to nature. For instance, marine mussels use multiple byssal threads to ensure attachment to rock surfaces, and octopus appendages make use of numerous suckers to efficiently capture preys. After the initial binding of an studies have demonstrated that conjugating multiple aptamers onto nanoparaptamer with its ligand, nearby aptamers can be readily recruited to facilitate additional ticles canthereby successfully provide resistance enzymatic degradation and increase binding, leading to a higher avidity.toPhysiological conditions present another nucleic challenge for aptamers; in their monomeric aptamers have shown to of be the rapidly acid stabilities due to increased local saltform, concentrations onbeen the surfaces nanopartidegraded by nuclease, a major drawback limiting their in vivo applications. Studies demonstrated that conjugating aptamers onto nanoparticles canmultivalent sucThehave current review focuses on the multiple structures and design principles of cessfully provide resistance to enzymatic degradation and increase nucleic acid stabilities aptamer approaches developed in recent years To this end, multivalent aptamers are first due to increased local salt concentrations on the surfaces of the nanoparticles [21,22]. Based on Aptamer their structures, multivalent aptamers can be generally divided into three
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