A Review: G-Quadruplex’s Applications in Biological Target Detection and Drug Delivery

Tian, Tian; Xiao, Heng; Zhou, Xiang

doi:10.2174/1568026615666150515151142

Cited by 19 publications

(14 citation statements)

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“…The impact of G4V on gene activity strongly suggests their biological and medical implications. The association of G4Vs with diseases and abnormal phenotypes is also of particular interest because G4 structures are therapeutic targets (52). A G4V may imply a gain or loss of a potential drug target in a specific group of people.…”

Section: Resultsmentioning

confidence: 99%

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G-quadruplex structural variations in human genome associated with single-nucleotide variations and their impact on gene activity

Gong

Wen

Tang

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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G-quadruplexes (G4s) formed by guanine-rich nucleic acids play a role in essential biological processes such as transcription and replication. Besides the >1.5 million putative G-4–forming sequences (PQSs), the human genome features >640 million single-nucleotide variations (SNVs), the most common type of genetic variation among people or populations. An SNV may alter a G4 structure when it falls within a PQS motif. To date, genome-wide PQS–SNV interactions and their impact have not been investigated. Herein, we present a study on the PQS–SNV interactions and the impact they can bring to G4 structures and, subsequently, gene expressions. Based on build 154 of the Single Nucleotide Polymorphism Database (dbSNP), we identified 5 million gains/losses or structural conversions of G4s that can be caused by the SNVs. Of these G4 variations (G4Vs), 3.4 million are within genes, resulting in an average load of >120 G4Vs per gene, preferentially enriched near the transcription start site. Moreover, >80% of the G4Vs overlap with transcription factor–binding sites and >14% with enhancers, giving an average load of 3 and 7.5 for the two regulatory elements, respectively. Our experiments show that such G4Vs can significantly influence the expression of their host genes. These results reveal genome-wide G4Vs and their impact on gene activity, emphasizing an understanding of genetic variation, from a structural perspective, of their physiological function and pathological implications. The G4Vs may also provide a unique category of drug targets for individualized therapeutics, health risk assessment, and drug development.

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Section: Resultsmentioning

confidence: 99%

“…BIOCHEMISTRY therapeutics, health risk assessment, and drug development. For example, a disease-causing G4V suggests that the corresponding G4 structure may be relevant to and serve as a unique target for the disease (52). This information may help develop therapeutic approaches to such diseases in a specific population.…”

Section: Discussionmentioning

confidence: 99%

G-quadruplex structural variations in human genome associated with single-nucleotide variations and their impact on gene activity

Gong

Wen

Tang

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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“…Notably, the G-quadruplex was found to be in a special structural scaffold in the spinach aptamer that is essential for the ligand binding and fluorescence [60]. Recently, the sequence requirement for the fluorescence of spinach RNA was extensively studied [61], Figure 1D) have also been reported and reviewed elsewhere [71][72][73].…”

Section: G-quadruplexes As Molecular Tools For Biological Applicationsmentioning

confidence: 99%

G-Quadruplexes: Prediction, Characterization, and Biological Application

Kwok

Merrick

2017

Trends in Biotechnology

322

245

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Guanine (G)-rich sequences in nucleic acids can assemble into G-quadruplex structures that involve G-quartets linked by loop nucleotides. The structural and topological diversity of G-quadruplexes have attracted great attention for decades. Recent methodological advances have advanced the identification and characterization of G-quadruplexes in vivo as well as in vitro, and at a much higher resolution and throughput, which has greatly expanded our current understanding of G-quadruplex structure and function. Accumulating knowledge about the structural properties of G-quadruplexes has helped to design and develop a repertoire of molecular and chemical tools for biological applications. This review highlights how these exciting methods and findings have opened new doors to investigate the potential functions and applications of G-quadruplexes in basic and applied biosciences.

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“…Besides acting as potential targets, G4s can be used as molecular tools for diverse applications. It is worth noting that the structure of G4s has been identified in studies using combinatorial methods and the systematic evolution of ligands by exponential enrichment (SELEX) technique with the aim of developing aptamers for therapeutic and diagnostic purposes [38,39,40]. G4s provide extra chemical and thermal stability for aptamer-based therapeutics, and such aptamers have been successfully designed to target a number of HIV proteins [41,42], prion proteins [43], and anti-cancer targets [44,45].…”

Section: Introductionmentioning

confidence: 99%

G-Quadruplex-Based Fluorescent Turn-On Ligands and Aptamers: From Development to Applications

Umar

Chan

et al. 2019

Molecules

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Guanine (G)-quadruplexes (G4s) are unique nucleic acid structures that are formed by stacked G-tetrads in G-rich DNA or RNA sequences. G4s have been reported to play significant roles in various cellular events in both macro- and micro-organisms. The identification and characterization of G4s can help to understand their different biological roles and potential applications in diagnosis and therapy. In addition to biophysical and biochemical methods to interrogate G4 formation, G4 fluorescent turn-on ligands can be used to target and visualize G4 formation both in vitro and in cells. Here, we review several representative classes of G4 fluorescent turn-on ligands in terms of their interaction mechanism and application perspectives. Interestingly, G4 structures are commonly identified in DNA and RNA aptamers against targets that include proteins and small molecules, which can be utilized as G4 tools for diverse applications. We therefore also summarize the recent development of G4-containing aptamers and highlight their applications in biosensing, bioimaging, and therapy. Moreover, we discuss the current challenges and future perspectives of G4 fluorescent turn-on ligands and G4-containing aptamers.

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A Review: G-Quadruplex’s Applications in Biological Target Detection and Drug Delivery

Cited by 19 publications

References 0 publications

G-quadruplex structural variations in human genome associated with single-nucleotide variations and their impact on gene activity

G-quadruplex structural variations in human genome associated with single-nucleotide variations and their impact on gene activity

G-Quadruplexes: Prediction, Characterization, and Biological Application

G-Quadruplex-Based Fluorescent Turn-On Ligands and Aptamers: From Development to Applications

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