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 Current Advances in Aptamers for Cancer Diagnosis and Therapy

Cancers ◽  
2018 ◽  
Vol 10 (1) ◽  
pp. 9 ◽  
Author(s):  
Shin-ichiro Hori ◽  
Alberto Herrera ◽  
John Rossi ◽  
Jiehua Zhou
Keyword(s):  
Cancer Diagnosis ◽  
Biomarker Discovery ◽  
Selection Process ◽  
Three Dimensional ◽  
High Affinity ◽  
Diagnosis And Therapy ◽  
Target Molecules ◽  
Exponential Enrichment ◽  
Cancer Diagnosis And Therapy ◽  
Simple Selection

Nucleic acid aptamers are single-stranded oligonucleotides that interact with target molecules with high affinity and specificity in unique three-dimensional structures. Aptamers are generally isolated by a simple selection process called systematic evolution of ligands by exponential enrichment (SELEX) and then can be chemically synthesized and modified. Because of their high affinity and specificity, aptamers are promising agents for biomarker discovery, as well as cancer diagnosis and therapy. In this review, we present recent progress and challenges in aptamer and SELEX technology and highlight some representative applications of aptamers in cancer therapy.

scholarly journals Using Aptamers for Cancer Biomarker Discovery

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Yun Min Chang ◽  
Michael J. Donovan ◽  
Weihong Tan
Keyword(s):  
Iterative Method ◽  
Cancer Diagnosis ◽  
Biomarker Discovery ◽  
Clinical Medicine ◽  
High Specificity ◽  
Specific Target ◽  
Synthetic Dna ◽  
High Affinity ◽  
Systematic Evolution ◽  
Exponential Enrichment

Aptamers are single-stranded synthetic DNA- or RNA-based oligonucleotides that fold into various shapes to bind to a specific target, which includes proteins, metals, and molecules. Aptamers have high affinity and high specificity that are comparable to that of antibodies. They are obtained using iterative method, called (Systematic Evolution of Ligands by Exponential Enrichment) SELEX and cell-based SELEX (cell-SELEX). Aptamers can be paired with recent advances in nanotechnology, microarray, microfluidics, and other technologies for applications in clinical medicine. One particular area that aptamers can shed a light on is biomarker discovery. Biomarkers are important in diagnosis and treatment of cancer. In this paper, we will describe ways in which aptamers can be used to discover biomarkers for cancer diagnosis and therapeutics.

scholarly journals Aptamer-iRNAs as Therapeutics for Cancer Treatment

2018 ◽  
Vol 11 (4) ◽  
pp. 108 ◽  
Author(s):  
Mario Soldevilla ◽  
Daniel Meraviglia-Crivelli de Caso ◽  
Ashwathi Menon ◽  
Fernando Pastor
Keyword(s):  
Cancer Therapy ◽  
Cancer Treatment ◽  
Antisense Oligonucleotides ◽  
Tertiary Structure ◽  
Potential Treatment ◽  
High Affinity ◽  
Different Types ◽  
Systematic Evolution ◽  
Exponential Enrichment ◽  
Selection Of

Aptamers are single-stranded oligonucleotides (ssDNA or ssRNA) that bind and recognize their targets with high affinity and specificity due to their complex tertiary structure. Aptamers are selected by a method called SELEX (Systematic Evolution of Ligands by EXponential enrichment). This method has allowed the selection of aptamers to different types of molecules. Since then, many aptamers have been described for the potential treatment of several diseases including cancer. It has been described over the last few years that aptamers represent a very useful tool as therapeutics, especially for cancer therapy. Aptamers, thanks to their intrinsic oligonucleotide nature, present inherent advantages over other molecules, such as cell-based products. Owing to their higher tissue penetrability, safer profile, and targeting capacity, aptamers are likely to become a novel platform for the delivery of many different types of therapeutic cargos. Here we focus the review on interfering RNAs (iRNAs) as aptamer-based targeting delivered agents. We have gathered the most reliable information on aptamers as targeting and carrier agents for the specific delivery of siRNAs, shRNA, microRNAs, and antisense oligonucleotides (ASOs) published in the last few years in the context of cancer therapy.

scholarly journals Preparation of a Specific ssDNA Aptamer for Brevetoxin-2 Using SELEX

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Rui-Yun Tian ◽  
Chao Lin ◽  
Shi-Yu Yu ◽  
Sheng Gong ◽  
Pan Hu ◽  
...  
Keyword(s):  
Research Direction ◽  
High Affinity ◽  
Complex Processes ◽  
Ssdna Aptamer ◽  
Coefficient Corrélation ◽  
Recognition Probe ◽  
Detection Probe ◽  
Systematic Evolution ◽  
Alternative Detection ◽  
Exponential Enrichment

The existing assays for detecting brevetoxin (BTX) depend on expensive equipment with a professional operator or on an antibody with limited stability, which requires complex processes, a high cost, and a considerable amount of time. The development of an alternative detection probe is another promising research direction. This paper reports the use of aptamers binding to BTX-2 in an analytical assay using the systematic evolution of ligands by exponential enrichment (SELEX). After 12 rounds of selection, the secondary structures of 25 sequences were predicted. Compared to other aptamers, Bap5 has relatively high affinity with the lowest dissociation constant of 4.83 μM, and IC50is 73.81 ng mL−1. A good linear regression formula ofy=30.688x-7.329with a coefficient correlation ofR2= 0.9798 was obtained using a biotin-avidin ELISA. Moreover, there is no cross-reaction with the detected marine toxins, except for BTX-2. Thus, Bap5 has potential to detect BTX-2 in shellfish in the future as a substitute for the recognition probe.

scholarly journals Specific inhibition of FGF5-induced cell proliferation by RNA aptamers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryo Amano ◽  
Masato Namekata ◽  
Masataka Horiuchi ◽  
Minami Saso ◽  
Takuya Yanagisawa ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Surface Plasmon Resonance ◽  
Growth Factor ◽  
Hair Growth ◽  
Rna Aptamers ◽  
Specific Inhibition ◽  
Fibroblast Growth ◽  
High Affinity ◽  
Systematic Evolution ◽  
Exponential Enrichment

AbstractFibroblast growth factor 5 (FGF5) is a crucial regulator of hair growth and an oncogenic factor in several human cancers. To generate FGF5 inhibitors, we performed Systematic Evolution of Ligands by EXponential enrichment and obtained novel RNA aptamers that have high affinity to human FGF5. These aptamers inhibited FGF5-induced cell proliferation, but did not inhibit FGF2-induced cell proliferation. Surface plasmon resonance demonstrated that one of the aptamers, F5f1, binds to FGF5 tightly (Kd = 0.7 ± 0.2 nM), but did not fully to FGF1, FGF2, FGF4, FGF6, or FGFR1. Based on sequence and secondary structure similarities of the aptamers, we generated the truncated aptamer, F5f1_56, which has higher affinity (Kd = 0.118 ± 0.003 nM) than the original F5f1. Since the aptamers have high affinity and specificity to FGF5 and inhibit FGF5-induced cell proliferation, they may be candidates for therapeutic use with FGF5-related diseases or hair disorders.

scholarly journals An Evolutionary/Biochemical Connection between Promoter- and Primer-Dependent Polymerases Revealed by Systematic Evolution of Ligands by Exponential Enrichment

2018 ◽  
Vol 200 (7) ◽  
Author(s):  
Katherine J. Fenstermacher ◽  
Vasudevan Achuthan ◽  
Thomas D. Schneider ◽  
Jeffrey J. DeStefano
Keyword(s):  
Core Promoter ◽  
Dna Polymerases ◽  
Promoter Sequence ◽  
Rna Polymerases ◽  
Sequence Specificity ◽  
High Affinity ◽  
Phage T7 ◽  
Systematic Evolution ◽  
Exponential Enrichment ◽  
Dna Primers

ABSTRACTDNA polymerases (DNAPs) recognize 3′ recessed termini on duplex DNA and carry out nucleotide catalysis. Unlike promoter-specific RNA polymerases (RNAPs), no sequence specificity is required for binding or initiation of catalysis. Despite this, previous results indicate that viral reverse transcriptases bind much more tightly to DNA primers that mimic the polypurine tract. In the current report, primer sequences that bind with high affinity toTaqand Klenow polymerases were identified using a modified systematic evolution of ligands by exponential enrichment (SELEX) approach. TwoTaq-specific primers that bound ∼10 (Taq1) and over 100 (Taq2) times more stably than controls toTaqwere identified. TaqI contained 8 nucleotides (5′-CACTAAAG-3′) that matched the phage T3 RNAP “core” promoter. Both primers dramatically outcompeted primers with similar binding thermodynamics in PCRs. Similarly, exonuclease−Klenow polymerase also selected a high-affinity primer that contained a related core promoter sequence from phage T7 RNAP (5′-ACTATAG-3′). For bothTaqand Klenow, even small modifications to the sequence resulted in large losses in binding affinity, suggesting that binding was highly sequence specific. The results are discussed in the context of possible effects on multiprimer (multiplex) PCR assays, molecular information theory, and the evolution of RNAPs and DNAPs.IMPORTANCEThis work further demonstrates that primer-dependent DNA polymerases can have strong sequence biases leading to dramatically tighter binding to specific sequences. These may be related to biological function or be a consequence of the structural architecture of the enzyme. New sequence specificity forTaqand Klenow polymerases were uncovered, and among them were sequences that contained the core promoter elements from T3 and T7 phage RNA polymerase promoters. This suggests the intriguing possibility that phage RNA polymerases exploited intrinsic binding affinities of ancestral DNA polymerases to develop their promoters. Conversely, DNA polymerases could have evolved from related RNA polymerases and retained the intrinsic binding preference despite there being no clear function for such a preference in DNA biology.

Development of a Subtype-Specific Diagnostic System for Influenza Virus H3N2 Using a Novel Virus-Based Systematic Evolution of Ligands by Exponential Enrichment (Viro-SELEX)

2019 ◽  
Vol 15 (7) ◽  
pp. 1609-1621 ◽  
Author(s):  
Junyoung Kwon ◽  
Chandan Narayan ◽  
Chonsaeng Kim ◽  
Min Jung Han ◽  
Meehyein Kim ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Point Of Care ◽  
Diagnostic System ◽  
Molecular Probes ◽  
Target Protein ◽  
Enveloped Virus ◽  
Novel Approach ◽  
Target Molecules ◽  
Systematic Evolution ◽  
Exponential Enrichment

Aptamers are oligonucleotide molecules that bind to specific target molecules generated by systematic evolution of ligands by exponential enrichment (SELEX). Aptamers have high future potential for use in diagnostics and therapeutics as molecular probes that recognize target molecules. To develop aptamers against a target protein using a SELEX process, it is necessary to purify the target protein. Purifying a membrane protein, however, is usually a challenging task. Here, we report a novel approach to developing aptamers against membrane proteins. Surrogate viruses containing target proteins on the surface of an enveloped virus (e.g., baculovirus), instead of purified proteins, were used in a new SELEX process. We designated this new SELEX process as "surrogate virus-based SELEX (viro-SELEX)." Using viro-SELEX, we developed a pair of aptamers that specifically interact with the hemagglutinin protein of influenza subtype H3N2. Using the aptamer pair and a lateral flow assay system, we developed a very sensitive point-of-care diagnostic system for specifically detecting influenza virus subtype H3N2.

Recent Advances in Colorectal Cancer-Specific Nucleic Acid Aptamers for Diagnostic and Therapeutic Applications

2020 ◽  
Vol 12 (1) ◽  
pp. 38-43
Author(s):  
Linlin Zhou ◽  
Mengdie Zou ◽  
Wanming Li
Keyword(s):  
Colorectal Cancer ◽  
Cancer Diagnosis ◽  
Chemical Properties ◽  
Tissue Penetration ◽  
Long Term Stability ◽  
Systematic Evolution ◽  
Exponential Enrichment ◽  
Cancer Diagnosis And Therapy ◽  
Single Stranded Oligonucleotide

Colorectal cancer is the third leading cause of cancer death, and its incidence is continuing to increase rapidly in developing countries. Thus, it is clinically important to achieve an early diagnosis and early treatment for colorectal cancer. Aptamers, also known as chemical antibodies, are short, single-stranded oligonucleotide ligands selected by systematic evolution of ligands by exponential enrichment (SELEX). Because of their excellent chemical properties, such as easy synthesis, controllable modifications, long-term stability, low immunogenicity, and fast tissue penetration, aptamers have good application prospects in cancer diagnosis as well as therapy, and some are in clinical trials. In this review, we discuss aptamers that have been developed for colorectal cancer, and then briefly highlight applications of aptamers in colorectal cancer diagnosis and therapy.

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