Chemical Modification of Aptamers for Increased Binding Affinity in Diagnostic Applications: Current Status and Future Prospects

Abstract

Aptamers are short single stranded DNA or RNA oligonucleotides that can recognize analytes with extraordinary target selectivity and affinity. Despite their promising properties and diagnostic potential, the number of commercial applications remains scarce. In order to endow them with novel recognition motifs and enhanced properties, chemical modification of aptamers has been pursued. This review focuses on chemical modifications, aimed at increasing the binding affinity for the aptamer’s target either in a non-covalent or covalent fashion, hereby improving their application potential in a diagnostic context. An overview of current methodologies will be given, thereby distinguishing between pre- and post-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) modifications.

Detection and beyond: challenges and advances in aptamer-based biosensors

“…Chemical modifications can be further performed after the SELEX process to fine-tune the aptamer properties. 31 For example, the SOMAmers initially selected to bind to plateletderived growth factor B (PDGF-BB) were further optimized by substituting the original modification (in this case, the benzyl group) with 14 alternative moieties. 32 By screening the best single substitutions, they could yield the modified aptamer that showed 5 times more improved binding to PDGF-BB than the unmodified aptamer.…”

Aptamers for Proteins Associated with Rheumatic Diseases: Progress, Challenges, and Prospects of Diagnostic and Therapeutic Applications

“…Some examples of chemical modifications of the aptamers described in this review are given in Figure 3 . A detailed discussion of aptamers’ chemical modifications can be found in recent comprehensive reviews [ 6 , 29 , 31 , 32 ].…”

“…( B ) An “inverted” 3′-thymidine attached by 3′-3′-phosphodiester linkage. ( C ) Examples of hydrophobic modifications of heterocyclic bases used in SOMAmers [ 29 ]. ( D ) Phosphorothioate analogs of oligodeoxyribonucleotides.…”

Recent Progress in the Identification of Aptamers Against Bacterial Origins and Their Diagnostic Applications

“…Many variations can be made to single-stranded DNA aptamers to ease their biosensing and diagnostic applications, for example, the 3′ or 5′ ends of the aptamers may be modified to carry tags. These modifications allow the DNA aptamers to fluoresce or generate redox reactions upon target bindings [ 16 ]. This article focuses on reviewing recently (mid-2015 to early 2020) reported new single-stranded DNA aptamers and their usage within bacterial biosensing and diagnostics, that aim to facilitate the detection of bacterial infections in humans.…”