G-Quadruplex-Forming Aptamers—Characteristics, Applications, and Perspectives

Abstract

G-quadruplexes constitute a unique class of nucleic acid structures formed by G-rich oligonucleotides of DNA- or RNA-type. Depending on their chemical nature, loops length, and localization in the sequence or structure molecularity, G-quadruplexes are highly polymorphic structures showing various folding topologies. They may be formed in the human genome where they are believed to play a pivotal role in the regulation of multiple biological processes such as replication, transcription, and translation. Thus, natural G-quadruplex structures became prospective targets for disease treatment. The fast development of systematic evolution of ligands by exponential enrichment (SELEX) technologies provided a number of G-rich aptamers revealing the potential of G-quadruplex structures as a promising molecular tool targeted toward various biologically important ligands. Because of their high stability, increased cellular uptake, ease of chemical modification, minor production costs, and convenient storage, G-rich aptamers became interesting therapeutic and diagnostic alternatives to antibodies. In this review, we describe the recent advances in the development of G-quadruplex based aptamers by focusing on the therapeutic and diagnostic potential of this exceptional class of nucleic acid structures.

Toward G-Quadruplex-Based Anticancer Agents: Biophysical and Biological Studies of Novel AS1411 Derivatives

“…Indeed, AS1411-GT-5′tr, which showed the best cytotoxic effect (together with AS1411-GT) on MCF-7 cells of all the GROs studied ( Table 4 ), turned out to be the most resistant to nuclease degradation. This is in agreement with the vast majority of published data indicating that only those GROs that are folded into stable G4 structures exhibit pronounced biological activity [ 6 , 7 , 66 , 67 ]. In addition, the hypothesis that GROs’ cytotoxic activity is not simply due to their interaction with nucleolin but to multi-targeted effects, including the targeting of other G4-recognizing proteins such as TOP1 [ 40 , 41 ], is once again supported by the data reported in this study.…”

“…Indeed, they can form G-quadruplexes (G4s), characteristic secondary structures composed of planar arrangements of four guanine (G) bases stabilized by eight Hoogsteen hydrogen bonds known as G-tetrads [ 5 ]. Interestingly, G4s are characterized by high thermodynamic stability, good resistance to numerous serum nucleases, increased cellular uptake, and ease of chemical synthesis and modification that make them an interesting alternative to antibodies and small molecules used in targeted therapy of cancer [ 6 ]. The pleiotropic properties of G4-forming GROs and their intrinsic high specificity against cancer cells, which is a general feature of most of the GROs studied so far, allowed to consider them as promising candidates for multi-targeted cancer therapy [ 4 , 7 ].…”

A G‐quadruplex‐forming RNA aptamer binds to the MTG8 TAFH domain and dissociates the leukemic AML1‐MTG8 fusion protein from DNA

“…To date, many G‐quadruplex aptamers have been obtained by SELEX against various targets [36]. For example, the HIV‐1 integrase‐binding aptamer comprising a single‐stranded DNA was shown by CD spectroscopy to fold into a G‐quadruplex [37].…”

The Potential of Telomeric G-Quadruplexes Containing Modified Oligoguanosine Overhangs in Activation of Bacterial Phagocytosis and Leukotriene Synthesis in Human Neutrophils

“…In the majority of examples, unfolding the G-quadruplex structure leads to the loss of biological activity of G-rich ODNs. G-quadruplex DNA aptamers become interesting therapeutic and diagnostic alternatives to antibodies because of their high thermal stability, resistance to numerous serum nucleases, increased cellular uptake, and ease of chemical modification [61]. In the context of our work, it should be noted that DNA G-tracts are recognized by scavenger receptors, which are expressed on the surface of immune cells and can act as phagocytic receptors, as well as TLR co-receptors facilitating ODN uptake [62,63].…”