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18 pages, 2745 KiB

Open AccessArticle

Analyzing Secondary Structure Patterns in DNA Aptamers Identified via CompELS

by Richard Sullivan, Mary Catherine Adams, Rajesh R. Naik and Valeria T. Milam

Molecules 2019, 24(8), 1572; https://doi.org/10.3390/molecules24081572 - 21 Apr 2019

Cited by 39 | Viewed by 8838

Abstract

In contrast to sophisticated high-throughput sequencing tools for genomic DNA, analytical tools for comparing secondary structure features between multiple single-stranded DNA sequences are less developed. For single-stranded nucleic acid ligands called aptamers, secondary structure is widely thought to play a pivotal role in [...] Read more.

In contrast to sophisticated high-throughput sequencing tools for genomic DNA, analytical tools for comparing secondary structure features between multiple single-stranded DNA sequences are less developed. For single-stranded nucleic acid ligands called aptamers, secondary structure is widely thought to play a pivotal role in driving recognition-based binding activity between an aptamer sequence and its specific target. Here, we employ a competition-based aptamer screening platform called CompELS to identify DNA aptamers for a colloidal target. We then analyze predicted secondary structures of the aptamers and a large population of random sequences to identify sequence features and patterns. Our secondary structure analysis identifies patterns ranging from position-dependent score matrixes of individual structural elements to position-independent consensus domains resulting from global alignment. Full article

(This article belongs to the Special Issue Oligonucleotides Application to Nano- and Biotechnology (DNA Origami, DNA Machine))

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16 pages, 3552 KiB

Open AccessArticle

Aptamer Efficacies for In Vitro and In Vivo Modulation of αC-Conotoxin PrXA Pharmacology

by Germain Sotoing Taiwe, Jérôme Montnach, Sébastien Nicolas, Stéphan De Waard, Emmanuelle Fiore, Eric Peyrin, Tarek Mohamed Abd El-Aziz, Muriel Amar, Jordi Molgó, Michel Ronjat, Denis Servent, Corinne Ravelet and Michel De Waard

Molecules 2019, 24(2), 229; https://doi.org/10.3390/molecules24020229 - 9 Jan 2019

Cited by 12 | Viewed by 3899

Abstract

The medical staff is often powerless to treat patients affected by drug abuse or misuse and poisoning. In the case of envenomation, the treatment of choice remains horse sera administration that poses a wealth of other medical conditions and threats. Previously, we have [...] Read more.

The medical staff is often powerless to treat patients affected by drug abuse or misuse and poisoning. In the case of envenomation, the treatment of choice remains horse sera administration that poses a wealth of other medical conditions and threats. Previously, we have demonstrated that DNA-based aptamers represent powerful neutralizing tools for lethal animal toxins of venomous origin. Herein, we further pursued our investigations in order to understand whether all toxin-interacting aptamers possessed equivalent potencies to neutralize αC-conotoxin PrXA in vitro and in vivo. We confirmed the high lethality in mice produced by αC-conotoxin PrXA regardless of the mode of injection and further characterized myoclonus produced by the toxin. We used high-throughput patch-clamp technology to assess the effect of αC-conotoxin PrXA on ACh-mediated responses in TE671 cells, responses that are carried by muscle-type nicotinic receptors. We show that 2 out of 4 aptamers reduce the affinity of the toxin for its receptor, most likely by interfering with the pharmacophore. In vivo, more complex responses on myoclonus and mice lethality are observed depending on the type of aptamer and mode of administration (concomitant or differed). Concomitant administration always works better than differed administration indicating the stability of the complex in vivo. The most remarkable conclusion is that an aptamer that has no or a limited efficacy in vitro may nevertheless be functional in vivo probably owing to an impact on the biodistribution or pharmacokinetics of the toxin in vivo. Overall, the results highlight that a blind selection of aptamers against toxins leads to efficient neutralizing compounds in vivo regardless of the mode of action. This opens the door to the use of aptamer mixtures as substitutes to horse sera for the neutralization of life-threatening animal venoms, an important WHO concern in tropical areas. Full article

(This article belongs to the Special Issue Oligonucleotides Application to Nano- and Biotechnology (DNA Origami, DNA Machine))

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8 pages, 1250 KiB

Open AccessFeature PaperArticle

S-Acyl-2-Thioethyl: A Convenient Base-Labile Protecting Group for the Synthesis of siRNAs Containing 5′-Vinylphosphonate

by Mehran Nikan, Wenyu Li, Garth A. Kinberger, Punit P. Seth, Eric E. Swayze and Thazha P. Prakash

Molecules 2019, 24(2), 225; https://doi.org/10.3390/molecules24020225 - 9 Jan 2019

Viewed by 4922

Abstract

We recently reported that (E)-5′-vinylphosphonate (5′-VP) is a metabolically-stable phosphate mimic for siRNA and demonstrated that 5′-VP improves the potency of the fully modified siRNAs in vivo. Here, we report an alternative synthesis of 5′-VP modified guide strand using S-pivaloyl-2-thioethyl [...] Read more.

We recently reported that (E)-5′-vinylphosphonate (5′-VP) is a metabolically-stable phosphate mimic for siRNA and demonstrated that 5′-VP improves the potency of the fully modified siRNAs in vivo. Here, we report an alternative synthesis of 5′-VP modified guide strand using S-pivaloyl-2-thioethyl (tBu-SATE) protecting group. The tBu-SATE group is readily removed during the final cleavage of the oligonucleotide from the solid support and providing a more convenient route for the synthesis of siRNA guide strand carrying a 5′-vinylphosphonate. Full article

(This article belongs to the Special Issue Oligonucleotides Application to Nano- and Biotechnology (DNA Origami, DNA Machine))

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15 pages, 3352 KiB

Open AccessArticle

Selection, Characterization, and Application of ssDNA Aptamer against Furaneol

by Natalia Komarova, Mariia Andrianova, Sergey Glukhov and Alexander Kuznetsov

Molecules 2018, 23(12), 3159; https://doi.org/10.3390/molecules23123159 - 30 Nov 2018

Cited by 32 | Viewed by 5232

Abstract

Furaneol is an aroma compound which occurs naturally in foods and is used as an artificial flavor. Detection of furaneol is required in food science and food processing industry. Capture- Systematic Evolution of Ligands by EXponential enrichment (SELEX) protocol was applied for the [...] Read more.

Furaneol is an aroma compound which occurs naturally in foods and is used as an artificial flavor. Detection of furaneol is required in food science and food processing industry. Capture- Systematic Evolution of Ligands by EXponential enrichment (SELEX) protocol was applied for the isolation of an aptamer binding to furaneol, a small volatile organic substance contributing to the flavor of various products. Thirteen cycles of selection were performed. The resulting DNA pool was cloned, using blunt-end cloning, and ninety-six plasmids were sequenced and analyzed. Eight oligonucleotides were selected as aptamer candidates and screened for the ability to bind to furaneol, using three different methods—magnetic-beads associated elution assay, SYBR Green I assay, and exonuclease protection assay. One of the candidates was further characterized as an aptamer. The apparent equilibrium constant was determined to be (1.1 ± 0.4) µM, by the fluorescent method. The reported aptamer was applied for development of the ion-sensitive field-effect transistor (ISFET)-based biosensor, for the analysis of furaneol, in the concentration range of 0.1–10 µM. Full article

(This article belongs to the Special Issue Oligonucleotides Application to Nano- and Biotechnology (DNA Origami, DNA Machine))

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10 pages, 1492 KiB

Open AccessArticle

A Label-Free Fluorescent DNA Calculator Based on Gold Nanoparticles for Sensitive Detection of ATP

by Jingjing Zhang, Shizhi Zhang, Chaoqun Niu, Chen Liu, Jie Du and Yong Chen

Molecules 2018, 23(10), 2494; https://doi.org/10.3390/molecules23102494 - 29 Sep 2018

Cited by 7 | Viewed by 3595

Abstract

Herein we described a deoxyribonucleic acid (DNA) calculator for sensitive detection of the determination of adenosine triphosphate (ATP) using gold nanoparticles (GNP) and PicoGreen fluorescence dye as signal transducer, and ATP and single-stranded DNA (DNA-M′) as activators. The calculator-related performances including linearity, reaction [...] Read more.

Herein we described a deoxyribonucleic acid (DNA) calculator for sensitive detection of the determination of adenosine triphosphate (ATP) using gold nanoparticles (GNP) and PicoGreen fluorescence dye as signal transducer, and ATP and single-stranded DNA (DNA-M′) as activators. The calculator-related performances including linearity, reaction time, logic gate, and selectivity were investigated, respectively. The results revealed that this oligonucleotide sensor was highly sensitive and selective. The detection range was 50–500 nmol/L (R² = 0.99391) and the detection limit was 46.5 nmol/L. The AND DNA calculator was successfully used for the ATP detection in human urine. Compared with other methods, this DNA calculator has the characteristics of being label-free, non-enzymic, simple, and highly sensitive. Full article

(This article belongs to the Special Issue Oligonucleotides Application to Nano- and Biotechnology (DNA Origami, DNA Machine))

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14 pages, 4009 KiB

Open AccessFeature PaperCommunication

Shaping Rolling Circle Amplification Products into DNA Nanoparticles by Incorporation of Modified Nucleotides and Their Application to In Vitro and In Vivo Delivery of a Photosensitizer

by Kyoung-Ran Kim, Pascal Röthlisberger, Seong Jae Kang, Kihwan Nam, Sangyoup Lee, Marcel Hollenstein and Dae-Ro Ahn

Molecules 2018, 23(7), 1833; https://doi.org/10.3390/molecules23071833 - 23 Jul 2018

Cited by 12 | Viewed by 10099

Abstract

Rolling circle amplification (RCA) is a robust way to generate DNA constructs, which are promising materials for biomedical applications including drug delivery because of their high biocompatibility. To be employed as a drug delivery platform, however, the DNA materials produced by RCA need [...] Read more.

Rolling circle amplification (RCA) is a robust way to generate DNA constructs, which are promising materials for biomedical applications including drug delivery because of their high biocompatibility. To be employed as a drug delivery platform, however, the DNA materials produced by RCA need to be shaped into nanoparticles that display both high cellular uptake efficiency and nuclease resistance. Here, we showed that the DNA nanoparticles (DNPs) can be prepared with RCA and modified nucleotides that have side-chains appended on the nucleobase are capable of interacting with the DNA strands of the resulting RCA products. The incorporation of the modified nucleotides improved cellular uptake efficiency and nuclease resistance of the DNPs. We also demonstrated that these DNPs could be employed as carriers for the delivery of a photosensitizer into cancer cells to achieve photodynamic therapy upon irradiation at both the in vitro and in vivo levels. Full article

(This article belongs to the Special Issue Oligonucleotides Application to Nano- and Biotechnology (DNA Origami, DNA Machine))

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10 pages, 2928 KiB

Open AccessFeature PaperArticle

Aptamer Display on Diverse DNA Polyhedron Supports

by Simon Chi-Chin Shiu, Lewis A. Fraser, Yifan Ding and Julian A. Tanner

Molecules 2018, 23(7), 1695; https://doi.org/10.3390/molecules23071695 - 11 Jul 2018

Cited by 15 | Viewed by 6152

Abstract

DNA aptamers are important tools for molecular recognition, particularly for a new generation of tools for biomedicine based on nucleic acid nanostructures. Here, we investigated the relative abilities of different shapes and sizes of DNA polyhedra to display an aptamer which binds to [...] Read more.

DNA aptamers are important tools for molecular recognition, particularly for a new generation of tools for biomedicine based on nucleic acid nanostructures. Here, we investigated the relative abilities of different shapes and sizes of DNA polyhedra to display an aptamer which binds to the malaria biomarker Plasmodium falciparum lactate dehydrogenase (PfLDH). The aptamer was shown to perform an Aptamer-Tethered Enzyme Capture (APTEC) assay with the hypothesis that the display of the aptamer above the surface through the use of a polyhedron may lead to better sensitivity than use of the aptamer alone. We compared different numbers of points of contact, different shapes, including tetrahedron, square, and pentagon-based pyramids, as well as prisms. We also investigated the optimal height of display of the structure. Our results demonstrated that the display of an aptamer on an optimized nanostructure improved sensitivity up to 6-fold relative to the aptamer alone in the APTEC assay. Other important factors included multiple basal points of contact with the surface, a tetrahedron proved superior to the more complex shaped structures, and height above the surface only made minor differences to efficacy. The display of an aptamer on a nanostructure may be beneficial for higher sensitivity aptamer-mediated malaria diagnosis. Aptamer displays using DNA nanostructure polyhedron supports could be a useful approach in a variety of applications. Full article

(This article belongs to the Special Issue Oligonucleotides Application to Nano- and Biotechnology (DNA Origami, DNA Machine))

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Review

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16 pages, 1535 KiB

Open AccessReview

Oligonucleotides Targeting Telomeres and Telomerase in Cancer

by Zachary Schrank, Nabiha Khan, Chike Osude, Sanjana Singh, Rachel J. Miller, Collin Merrick, Alexander Mabel, Adijan Kuckovic and Neelu Puri

Molecules 2018, 23(9), 2267; https://doi.org/10.3390/molecules23092267 - 5 Sep 2018

Cited by 39 | Viewed by 11056

Abstract

Telomeres and telomerase have become attractive targets for the development of anticancer therapeutics due to their involvement in cancer cell immortality. Currently, several therapeutics have been developed that directly target telomerase and telomeres, such as telomerase inhibitors and G-quadruplex stabilizing ligands. Telomere-specific oligonucleotides [...] Read more.

Telomeres and telomerase have become attractive targets for the development of anticancer therapeutics due to their involvement in cancer cell immortality. Currently, several therapeutics have been developed that directly target telomerase and telomeres, such as telomerase inhibitors and G-quadruplex stabilizing ligands. Telomere-specific oligonucleotides that reduce telomerase activity and disrupt telomere architecture are also in development as novel anticancer therapeutics. Specifically, GRN163L and T-oligos have demonstrated promising anticancer activity in multiple cancers types via induction of potent DNA damage responses. Currently, several miRNAs have been implicated in the regulation of telomerase activity and may prove to be valuable targets in the development of novel therapies by reducing expression of telomerase subunits. Targeting miRNAs that are known to increase expression of telomerase subunits may be another strategy to reduce carcinogenesis. This review aims to provide a comprehensive understanding of current oligonucleotide-based anticancer therapies that target telomeres and telomerase. These studies may help design novel therapeutic approaches to overcome the challenges of oligonucleotide therapy in a clinical setting. Full article

(This article belongs to the Special Issue Oligonucleotides Application to Nano- and Biotechnology (DNA Origami, DNA Machine))

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14 pages, 5189 KiB

Open AccessReview

DNA Origami Nanomachines

by Masayuki Endo and Hiroshi Sugiyama

Molecules 2018, 23(7), 1766; https://doi.org/10.3390/molecules23071766 - 18 Jul 2018

Cited by 65 | Viewed by 12569

Abstract

DNA can assemble various molecules and nanomaterials in a programmed fashion and is a powerful tool in the nanotechnology and biology research fields. DNA also allows the construction of desired nanoscale structures via the design of DNA sequences. Structural nanotechnology, especially DNA origami, [...] Read more.

DNA can assemble various molecules and nanomaterials in a programmed fashion and is a powerful tool in the nanotechnology and biology research fields. DNA also allows the construction of desired nanoscale structures via the design of DNA sequences. Structural nanotechnology, especially DNA origami, is widely used to design and create functionalized nanostructures and devices. In addition, DNA molecular machines have been created and are operated by specific DNA strands and external stimuli to perform linear, rotational, and reciprocating movements. Furthermore, complicated molecular systems have been created on DNA nanostructures by arranging multiple molecules and molecular machines precisely to mimic biological systems. Currently, DNA nanomachines, such as molecular motors, are operated on DNA nanostructures. Dynamic DNA nanostructures that have a mechanically controllable system have also been developed. In this review, we describe recent research on new DNA nanomachines and nanosystems that were built on designed DNA nanostructures. Full article

(This article belongs to the Special Issue Oligonucleotides Application to Nano- and Biotechnology (DNA Origami, DNA Machine))

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34 pages, 33029 KiB

Open AccessReview

Applications of Ruthenium Complexes Covalently Linked to Nucleic Acid Derivatives

by Marie Flamme, Emma Clarke, Gilles Gasser and Marcel Hollenstein

Molecules 2018, 23(7), 1515; https://doi.org/10.3390/molecules23071515 - 22 Jun 2018

Cited by 21 | Viewed by 6240

Abstract

Oligonucleotides are biopolymers that can be easily modified at various locations. Thereby, the attachment of metal complexes to nucleic acid derivatives has emerged as a common pathway to improve the understanding of biological processes or to steer oligonucleotides towards novel applications such as [...] Read more.

Oligonucleotides are biopolymers that can be easily modified at various locations. Thereby, the attachment of metal complexes to nucleic acid derivatives has emerged as a common pathway to improve the understanding of biological processes or to steer oligonucleotides towards novel applications such as electron transfer or the construction of nanomaterials. Among the different metal complexes coupled to oligonucleotides, ruthenium complexes, have been extensively studied due to their remarkable properties. The resulting DNA-ruthenium bioconjugates have already demonstrated their potency in numerous applications. Consequently, this review focuses on the recent synthetic methods developed for the preparation of ruthenium complexes covalently linked to oligonucleotides. In addition, the usefulness of such conjugates will be highlighted and their applications from nanotechnologies to therapeutic purposes will be discussed. Full article

(This article belongs to the Special Issue Oligonucleotides Application to Nano- and Biotechnology (DNA Origami, DNA Machine))

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