scholarly journals Aptamers as Both Drugs and Drug-Carriers

2014 ◽  
Vol 2014 ◽  
pp. 1-21 ◽  
Author(s):  
Md. Ashrafuzzaman
Keyword(s):  
Nucleic Acid ◽  
Specific Binding ◽  
Drug Carriers ◽  
Diagnostic Tools ◽  
Computational Techniques ◽  
Biophysical Properties ◽  
Binding Properties ◽  
Systematic Evolution ◽  
Exponential Enrichment ◽  
Novel Drug

Aptamers are short nucleic acid oligos. They may serve as both drugs and drug-carriers. Their use as diagnostic tools is also evident. They can be generated using various experimental, theoretical, and computational techniques. The systematic evolution of ligands by exponential enrichment which uses iterative screening of nucleic acid libraries is a popular experimental technique. Theory inspired methodology entropy-based seed-and-grow strategy that designs aptamer templates to bind specifically to targets is another one. Aptamers are predicted to be highly useful in producing general drugs and theranostic drugs occasionally for certain diseases like cancer, Alzheimer’s disease, and so on. They bind to various targets like lipids, nucleic acids, proteins, small organic compounds, and even entire organisms. Aptamers may also serve as drug-carriers or nanoparticles helping drugs to get released in specific target regions. Due to better target specific physical binding properties aptamers cause less off-target toxicity effects. Therefore, search for aptamer based drugs, drug-carriers, and even diagnostic tools is expanding fast. The biophysical properties in relation to the target specific binding phenomena of aptamers, energetics behind the aptamer transport of drugs, and the consequent biological implications will be discussed. This review will open up avenues leading to novel drug discovery and drug delivery.

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

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3781 ◽  
Author(s):  
Carolina Roxo ◽  
Weronika Kotkowiak ◽  
Anna Pasternak
Keyword(s):  
Nucleic Acid ◽  
Production Costs ◽  
Biological Processes ◽  
Disease Treatment ◽  
Diagnostic Potential ◽  
G Quadruplex ◽  
Fast Development ◽  
Systematic Evolution ◽  
Nucleic Acid Structures ◽  
Exponential Enrichment

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.

scholarly journals Aptamers, the Nucleic Acid Antibodies, in Cancer Therapy

2020 ◽  
Vol 21 (8) ◽  
pp. 2793 ◽  
Author(s):  
Zhaoying Fu ◽  
Jim Xiang
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
Cancer Therapy ◽  
Specific Binding ◽  
High Specificity ◽  
Medical Community ◽  
Therapeutic Uses ◽  
Repeated Use ◽  
Systematic Evolution ◽  
Exponential Enrichment

The arrival of the monoclonal antibody (mAb) technology in the 1970s brought with it the hope of conquering cancers to the medical community. However, mAbs, on the whole, did not achieve the expected wonder in cancer therapy although they do have demonstrated successfulness in the treatment of a few types of cancers. In 1990, another technology of making biomolecules capable of specific binding appeared. This technique, systematic evolution of ligands by exponential enrichment (SELEX), can make aptamers, single-stranded DNAs or RNAs that bind targets with high specificity and affinity. Aptamers have some advantages over mAbs in therapeutic uses particularly because they have little or no immunogenicity, which means the feasibility of repeated use and fewer side effects. In this review, the general properties of the aptamer, the advantages and limitations of aptamers, the principle and procedure of aptamer production with SELEX, particularly the undergoing studies in aptamers for cancer therapy, and selected anticancer aptamers that have entered clinical trials or are under active investigations are summarized.

scholarly journals Implementation of High-Throughput Sequencing (HTS) in Aptamer Selection Technology

2020 ◽  
Vol 21 (22) ◽  
pp. 8774
Author(s):  
Natalia Komarova ◽  
Daria Barkova ◽  
Alexander Kuznetsov
Keyword(s):  
Nucleic Acid ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Combinatorial Libraries ◽  
Structure And Function ◽  
Huge Number ◽  
Systematic Evolution ◽  
And Function ◽  
Exponential Enrichment

Aptamers are nucleic acid ligands that bind specifically to a target of interest. Aptamers have gained in popularity due to their high potential for different applications in analysis, diagnostics, and therapeutics. The procedure called systematic evolution of ligands by exponential enrichment (SELEX) is used for aptamer isolation from large nucleic acid combinatorial libraries. The huge number of unique sequences implemented in the in vitro evolution in the SELEX process imposes the necessity of performing extensive sequencing of the selected nucleic acid pools. High-throughput sequencing (HTS) meets this demand of SELEX. Analysis of the data obtained from sequencing of the libraries produced during and after aptamer isolation provides an informative basis for precise aptamer identification and for examining the structure and function of nucleic acid ligands. This review discusses the technical aspects and the potential of the integration of HTS with SELEX.

Modified Nucleic Acid for Systematic Evolution of RNA Ligands by Exponential Enrichment

1998 ◽  
Vol 13 (2) ◽  
pp. 114-123 ◽  
Author(s):  
Yoshihiro Ito ◽  
Naozumi Teramoto ◽  
Naoki Kawazoe ◽  
Kojiro Inada ◽  
Yukio Imanishi
Keyword(s):  
Nucleic Acid ◽  
Systematic Evolution ◽  
Rna Ligands ◽  
Exponential Enrichment

The Arabidopsis class I TCP transcription factor AtTCP11 is a developmental regulator with distinct DNA-binding properties due to the presence of a threonine residue at position 15 of the TCP domain

2011 ◽  
Vol 435 (1) ◽  
pp. 143-155 ◽  
Author(s):  
Ivana L. Viola ◽  
Nora G. Uberti Manassero ◽  
Rodrigo Ripoll ◽  
Daniel H. Gonzalez
Keyword(s):  
Dna Binding ◽  
Binding Sites ◽  
Class I ◽  
Binding Properties ◽  
Threonine Residue ◽  
Dna Binding Specificity ◽  
Systematic Evolution ◽  
Enrichment Experiments ◽  
Exponential Enrichment ◽  
Dna Binding Properties

The TCP domain is a DNA-binding domain present in plant transcription factors that modulate different processes. In the present study, we show that Arabidopsis class I TCP proteins are able to interact with a dyad-symmetric sequence composed of two GTGGG half-sites. TCP20 establishes symmetric interactions with the 5′ half of each strand, whereas TCP11 interacts mainly with the 3′ half. SELEX (systematic evolution of ligands by exponential enrichment) experiments with TCP15 and TCP20 indicated that these proteins have similar, although not identical, DNA-binding preferences and are able to interact with non-palindromic binding sites of the type GTGGGNCCNN. TCP11 shows a different DNA-binding specificity, with a preference for the sequence GTGGGCCNNN. The distinct DNA-binding properties of TCP11 are due to the presence of a threonine residue at position 15 of the TCP domain, a position that is occupied by an arginine residue in most TCP proteins. TCP11 also forms heterodimers with TCP15 that have increased DNA-binding efficiency. The expression in plants of a repressor form of TCP11 demonstrated that this protein is a developmental regulator that influences the growth of leaves, stems and petioles, and pollen development. The results suggest that changes in DNA-binding preferences may be one of the mechanisms through which class I TCP proteins achieve functional specificity.

scholarly journals Bioapplications of Cell-SELEX-Generated Aptamers in Cancer Diagnostics, Therapeutics, Theranostics and Biomarker Discovery: A Comprehensive Review

Cancers ◽  
2018 ◽  
Vol 10 (2) ◽  
pp. 47 ◽  
Author(s):  
Xuehui Pang ◽  
Cheng Cui ◽  
Shuo Wan ◽  
Ying Jiang ◽  
Liangliang Zhang ◽  
...  
Keyword(s):  
Biomarker Discovery ◽  
Drug Carriers ◽  
Cancer Diagnostics ◽  
High Affinity ◽  
Protein Receptors ◽  
Target Molecules ◽  
Systematic Evolution ◽  
Multifunctional Molecules ◽  
Exponential Enrichment ◽  
Single Stranded Oligonucleotide

Currently, functional single-stranded oligonucleotide probes, termed aptamers, generated by an iterative technology, Systematic Evolution of Ligands by Exponential Enrichment (SELEX), are utilized to selectively target molecules or cells with high affinity. Aptamers hold considerable promise as multifunctional molecules or conjugates for challenging nanotechnologies or bioapplications now and in the future. In this review, we first describe recent endeavors to select aptamers towards live cancer cells via cell-SELEX. We then introduce several characteristic applications of selected aptamers, especially in imaging, drug delivery and therapy. In part, these advances have been made possible via synthesis of aptamer-based nanomaterials, which, by their sizes, shapes, and physicochemical properties, allow such aptamer-nanomaterial complexes to function as signal reporters or drug carriers. We also describe how these aptamer-based molecular tools contribute to cancer biomarker discovery through high-affinity recognition of membrane protein receptors.

scholarly journals Molecular Modeling Applied to Nucleic Acid-Based Molecule Development

Biomolecules ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 83 ◽  
Author(s):  
Arne Krüger ◽  
Flávia Zimbres ◽  
Thales Kronenberger ◽  
Carsten Wrenger
Keyword(s):  
Molecular Modeling ◽  
Nucleic Acid ◽  
Small Molecules ◽  
Structure Prediction ◽  
Rna Sequences ◽  
The Past ◽  
Enrichment Technique ◽  
Systematic Evolution ◽  
Exponential Enrichment ◽  
Early Drug

Molecular modeling by means of docking and molecular dynamics (MD) has become an integral part of early drug discovery projects, enabling the screening and enrichment of large libraries of small molecules. In the past decades, special emphasis was drawn to nucleic acid (NA)-based molecules in the fields of therapy, diagnosis, and drug delivery. Research has increased dramatically with the advent of the SELEX (systematic evolution of ligands by exponential enrichment) technique, which results in single-stranded DNA or RNA sequences that bind with high affinity and specificity to their targets. Herein, we discuss the role and contribution of docking and MD to the development and optimization of new nucleic acid-based molecules. This review focuses on the different approaches currently available for molecular modeling applied to NA interaction with proteins. We discuss topics ranging from structure prediction to docking and MD, highlighting their main advantages and limitations and the influence of flexibility on their calculations.

scholarly journals Inside the Black Box: What Makes SELEX Better?

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3598 ◽  
Author(s):  
Natalia Komarova ◽  
Alexander Kuznetsov
Keyword(s):  
Nucleic Acid ◽  
Selection Process ◽  
Combinatorial Libraries ◽  
Black Box ◽  
Aptamer Selection ◽  
Selection Protocol ◽  
Systematic Evolution ◽  
Exponential Enrichment

Aptamers are small oligonucleotides that are capable of binding specifically to a target, with impressive potential for analysis, diagnostics, and therapeutics applications. Aptamers are isolated from large nucleic acid combinatorial libraries using an iterative selection process called SELEX (Systematic Evolution of Ligands by EXponential enrichment). Since being implemented 30 years ago, the SELEX protocol has undergone many modifications and improvements, but it remains a laborious, time-consuming, and costly method, and the results are not always successful. Each step in the aptamer selection protocol can influence its results. This review discusses key technical points of the SELEX procedure and their influence on the outcome of aptamer selection.

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