Systematic Evolution of Ligands by Exponential Enrichment Technologies and Aptamer-Based Applications: Recent Progress and Challenges in Precision Medicine of Infectious Diseases

Xu, Yixin; Xin, Jiang; Zhou, Yanhong; Ma, Ming; Wang, Minjin; Ying, Binwu

doi:10.3389/fbioe.2021.704077

Cited by 33 publications

(21 citation statements)

References 192 publications

(161 reference statements)

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“…Exogenous G-rich oligomers forming stable G4 structures under physiological conditions can recognize these proteins, acting as aptamers. Aptamers are usually created by selecting them from a large random sequence pool through Systematic Evolution of Ligands by EXponential enrichment (SELEX) [ 15 ]; however, it is possible to find them in their “natural form” in riboswitches [ 16 ]. Aptamers are artificial single-chained DNA or RNA oligonucleotides that are generally 20- to 80-nucleotides-long, which are able to adopt distinctive three-dimensional (3D) structures thanks to several intramolecular interactions [ 17 ], such as the very stable nucleic acid secondary conformations G4s in the presence of G-rich sequences and appropriate metal cations.…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative Effects of the Aptamer d(GGGT)4 and Its Analogues with an Abasic-Site Mimic Loop on Different Cancer Cells

Virgilio

Pecoraro

Benigno

et al. 2022

IJMS

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In this paper, we study the T30923 antiproliferative potential and the contribution of its loop residues in six different human cancer cell lines by preparing five T30923 variants using the single residue replacement approach of loop thymidine with an abasic site mimic (S). G-rich oligonucleotides (GRO) show interesting anticancer properties because of their capability to adopt G-quadruplex structures (G4s), such as the G4 HIV-1 integrase inhibitor T30923. Considering the multi-targeted effects of G4-aptamers and the limited number of cancer cell lines tested, particularly for T30923, it should be important to find a suitable tumor line, in addition to considering that the effects also strictly depend on G4s. CD, NMR and non-denaturating polyacrylamide gel electrophoresis data clearly show that all modified ODNs closely resemble the dimeric structure of parallel G4s’ parent aptamer, keeping the resistance in biological environments substantially unchanged, as shown by nuclease stability assay. The antiproliferative effects of T30923 and its variants are tried in vitro by MTT assays, showing interesting cytotoxic activity, depending on time and dose, for all G4s, especially in MDA-MB-231 cells with a reduction in cell viability approximately up to 30%. Among all derivatives, QS12 results are the most promising, showing more pronounced cytotoxic effects both in MDA-MB-231 and Hela cells, with a decrease in cell viability from 70% to 60%. In summary, the single loop residue S substitution approach may be useful for designing antiproliferative G4s, considering that most of them, characterized by single residue loops, may be able to bind different targets in several cancer cell pathways. Generally, this approach could be of benefit by revealing some minimal functional structures, stimulating further studies aimed at the development of novel anticancer drugs.

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Section: Introductionmentioning

confidence: 99%

Antiproliferative Effects of the Aptamer d(GGGT)4 and Its Analogues with an Abasic-Site Mimic Loop on Different Cancer Cells

Virgilio

Pecoraro

Benigno

et al. 2022

IJMS

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“…Parasitic diseases are still serious threats to human life and health, especially in underdeveloped countries and regions, there is an urgent need to study and explore new methods of diagnosis. In recent years, research reports have screened various aptamers that can specifically recognize schistosome eggs, 135 , 136 Leishmania in sandflies, 137 , 138 Plasmodium in blood, 139 , 140 , 141 and Plasmodium‐infected red blood cells. 142 , 143 They provide new avenues for the development of novel human parasite detection and control methods.…”

Section: Applications Of Aptamersmentioning

confidence: 99%

Aptamers: A prospective tool for infectious diseases diagnosis

Chen

Zhou

Peng

et al. 2022

Clinical Laboratory Analysis

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It is well known that people's health is seriously threatened by various pathogens (such as Mycobacterium tuberculosis, Treponema pallidum, Novel coronavirus, HIV, Mucor, etc.), which leads to heavy socioeconomic burdens. Therefore, early and accurate pathogen diagnosis is essential for timely and effective therapies. Up to now, diagnosing human contagious diseases at molecule and nano levels is remarkably difficult owing to insufficient valid probes when it comes to determining the biological markers of pathogens. Aptamers are a set of high‐specificity and high‐sensitivity plastic oligonucleotides screened in vitro via the selective expansion of ligands by exponential enrichment (SELEX). With the advent of aptamer‐based technologies, their merits have aroused mounting academic interest. In recent years, as new detection and treatment tools, nucleic acid aptamers have been extensively utilized in the field of biomedicine, such as pathogen detection, new drug development, clinical diagnosis, nanotechnology, etc. However, the traditional SELEX method is cumbersome and has a long screening cycle, and it takes several months to screen out aptamers with high specificity. With the persistent development of SELEX‐based aptamer screening technologies, the application scenarios of aptamers have become more and more extensive. The present research briefly reviews the research progress of nucleic acid aptamers in the field of biomedicine, especially in the diagnosis of contagious diseases.

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“…Aptamers are DNA- or RNA-based ligands, sometimes discovered by chance but more often identified through several combinatorial techniques collectively called SELEX (Systematic Evolution of Ligands by EXponential enrichment) [ 1 ]. Depending on their sequence, aptamers can generally adopt specific three-dimensional structures that allow them to interact with a given target with high affinity and specificity.…”

Section: Introductionmentioning

confidence: 99%

Properties and Potential Antiproliferative Activity of Thrombin-Binding Aptamer (TBA) Derivatives with One or Two Additional G-Tetrads

Benigno

Virgilio

Bello

et al. 2022

IJMS

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In this paper, we study the biological properties of two TBA analogs containing one and two extra G-tetrads, namely TBAG3 and TBAG4, respectively, and two further derivatives in which one of the small loops at the bottom (TBAG41S) or the large loop at the top (TBAG4GS) of the TBAG4 structure has been completely modified by replacing all loop residues with abasic site mimics. The therapeutical development of the TBA was hindered by its low thermodynamic and nuclease stability, while its potential as an anticancer/antiproliferative molecule is also affected by the anticoagulant activity, being a side effect in this case. In order to obtain suitable TBA analogs and to explore the involvement of specific aptamer regions in biological activity, the antiproliferative capability against DU 145 and MDAMB 231 cancer cell lines (MTT), the anticoagulant properties (PT), the biological degradability (nuclease stability assay) and nucleolin (NCL) binding ability (SPR) of the above described TBA derivatives have been tested. Interestingly, none of the TBA analogs exhibits an anticoagulant activity, while all of them show antiproliferative properties to the same extent. Furthermore, TBAG4 displays extraordinary nuclease stability and promising antiproliferative properties against breast cancer cells binding NCL efficiently. These results expand the range of G4-structures targeting NCL and the possibility of developing novel anticancer and antiviral drugs.

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Systematic Evolution of Ligands by Exponential Enrichment Technologies and Aptamer-Based Applications: Recent Progress and Challenges in Precision Medicine of Infectious Diseases

Cited by 33 publications

References 192 publications

Antiproliferative Effects of the Aptamer d(GGGT)4 and Its Analogues with an Abasic-Site Mimic Loop on Different Cancer Cells

Antiproliferative Effects of the Aptamer d(GGGT)4 and Its Analogues with an Abasic-Site Mimic Loop on Different Cancer Cells

Aptamers: A prospective tool for infectious diseases diagnosis

Properties and Potential Antiproliferative Activity of Thrombin-Binding Aptamer (TBA) Derivatives with One or Two Additional G-Tetrads

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