G-quadruplex-based aptamers against protein targets in therapy and diagnostics

Abstract

Nucleic acid aptamers are single-stranded DNA or RNA molecules identified to recognize with high affinity specific targets including proteins, small molecules, ions, whole cells and even entire organisms, such as viruses or bacteria. They can be identified from combinatorial libraries of DNA or RNA oligonucleotides by SELEX technology, an in vitro iterative selection procedure consisting of binding (capture), partitioning and amplification steps. Remarkably, many of the aptamers selected against biologically relevant protein targets are G-rich sequences that can fold into stable G-quadruplex (G4) structures. Aiming at disseminating novel inspiring ideas within the scientific community in the field of G4-structures, the emphasis of this review is placed on: 1) recent advancements in SELEX technology for the efficient and rapid identification of new candidate aptamers (introduction of microfluidic systems and next generation sequencing); 2) recurrence of G4 structures in aptamers selected by SELEX against biologically relevant protein targets; 3) discovery of several G4-forming motifs in important regulatory regions of the human or viral genome bound by endogenous proteins, which per se can result into potential aptamers; 4) an updated overview of G4-based aptamers with therapeutic potential and 5) a discussion on the most attractive G4-based aptamers for diagnostic applications. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.

In-depth Bioinformatic Analyses of Human SARS-CoV-2, SARS-CoV, MERS-CoV, and OtherNidoviralesSuggest Important Roles of Noncanonical Nucleic Acid Structures in Their Lifecycles

“…Various G-quadruplex-forming aptamers are used as drugs against many different viral proteins, suggesting a prominent role for QBPmediated regulation. Among many other viruses, in particular Hepatitis C virus, HIV-1, and SARS-CoV are targets of these G-quadruplex-forming aptamers (Platella et al, 2017). Quadruplex binding domain has been found in nonstructural protein 3 (Nsp3) (Lei et al, 2018).…”

Short Duplex Module Coupled to G-Quadruplexes Increases Fluorescence of Synthetic GFP Chromophore Analogues

“…Aptamers are DNA or RNA fragments that recognize their targets with high sensitivity and selectivity due to their unique three-dimensional structures that can be tuned using systematic evolution of ligands by exponential enrichment (SELEX) [1][2][3][4][5]. They have several advantages over antibodies, such as high stability, lack of immunogenicity, low molecular weight, simplicity of synthesis and chemical modification or conjugation.…”

Development of HGF‐binding aptamers with the combination of G4 promoter‐derived aptamer selection and in silico maturation

“…Aptamers have some advantages over antibodies in that they have good thermal stability, permit easy introduction of chemical modification, and can be easily produced by chemical synthesis. Due to these advantages, aptamers are increasingly gaining traction as molecular recognition elements of biosensors and in medical applications (Nguyen et al, 2017;Platella et al, 2017;Seo and Gu, 2017;Torres-Chavolla and Alocilja, 2009;Zhou and Rossi, 2017). Aptamers are generally selected by Systematic Evolution of Ligands by EXponential enrichment (SELEX) (Ellington and Szostak, 1990;Tuerk and Gold, 1990).…”