scholarly journals The Potential Use of Aptamers in The Process of Drug Development

2021 ◽  
Author(s):  
Tooba Gholikhani ◽  
Balam Jimenez Brito ◽  
Frey Livingston ◽  
Shalen Kumar
Keyword(s):  
Drug Discovery ◽  
High Specificity ◽  
Therapeutic Drug ◽  
3 Dimensional ◽  
Synthetic Oligonucleotide ◽  
Binding Agents ◽  
Systematic Evolution ◽  
Exponential Enrichment ◽  
Rational Process ◽  
Potential Use

Single-stranded nucleic acids can fold and create unique 3-dimensional structures when interacting with other molecules. The unique structure can achieve high specificity and affinity for the particular target. Synthetic oligonucleotide binding agents also known as aptamers are generated through the rational process of Systematic Evolution of Ligands by Exponential Enrichment (SELEX.) As this technology matures it shows increasing promise for use in the field of a therapeutic drug, drug discovery, development, and delivery, and this report seeks to detail how this technology may be applied.

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 Cell-SELEX-based aptamer-conjugated nanomaterials for cancer diagnosis and therapy

2015 ◽  
Vol 2 (1) ◽  
pp. 71-84 ◽  
Author(s):  
Hong-Min Meng ◽  
Ting Fu ◽  
Xiao-Bing Zhang ◽  
Weihong Tan
Keyword(s):  
Cancer Diagnosis ◽  
Metallic Nanoparticles ◽  
Carbon Nanomaterials ◽  
Polymeric Nanoparticles ◽  
High Specificity ◽  
Diagnosis And Therapy ◽  
Systematic Evolution ◽  
Exponential Enrichment ◽  
Cancer Diagnosis And Therapy ◽  
Significant Attention

Abstract Nucleic acid aptamers, which are generated by a novel technique called SELEX (systematic evolution of ligands by exponential enrichment), have recently attracted significant attention in the field of early detection and treatment of cancer based on their numerous merits, such as high affinity, high specificity, small size, little immunogenicity, stable structures, and ease of chemical modification. Furthermore, aptamers can gain more flexibility as cancer cell targeting tools when conjugated to nanomaterials, including metallic nanoparticles, carbon nanomaterials, DNA nanodevices, and polymeric nanoparticles. We discuss the progress achieved in cancer diagnosis and therapy through the conjugation of cell-SELEX-based aptamers with different nanomaterials.

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.

FEATURES OF ORGANOPHOSPHATES IMMOBILIZATION VIA STREPTAVIDIN-BIOTIN SYSTEM FOR EXPERIMENTS ON SELECTION OF APTAMERS

2020 ◽  
pp. 12-20
Author(s):  
D. A. Belinskaya ◽  
Yu. V. Chelusnova ◽  
V. V. Abzianidze ◽  
N. V. Goncharov
Keyword(s):  
Polyethylene Glycol ◽  
Organophosphorus Compounds ◽  
Binding Energies ◽  
Rna Aptamers ◽  
Main Method ◽  
Modeling Methods ◽  
Molecular Dynamics Methods ◽  
Systematic Evolution ◽  
Exponential Enrichment ◽  
Selection Of

Poisoning with organophosphorus compounds occupy one of the leading places in exotoxicosis. At the first stage, the detoxification of organophosphates can be provided with the help of DNA or RNA aptamers that bind the poison in the bloodstream. Currently, the main method of searching for aptamers is the experimental method of systematic evolution of ligands by exponential enrichment (SELEX). In the process of aptamer selection, the target molecule must be immobilized via the streptavidin-biotin complex. Since the poison molecule is small in size, to increase its availability for binding to aptamer, it is necessary to use a spacer between organophosphorus compounds and biotin. The aim of this work was to optimize the selection of aptamers for organophosphorus compounds by increasing the availability of a poison molecule immobilized via the streptavidin-biotin complex on the example of paraoxon. For this purpose, three spacers between organophosphorus compounds and biotin were tested using molecular modeling methods: three links of polyethylene glycol (3-PEG), four links of polyethylene glycol (4-PEG) and aminohexyl. The conformation of the biotinylated paraoxon complex with streptavidin and the interaction of paraoxon with the binding fragment of the aptamer were modeled using molecular docking and molecular dynamics methods. The ability of biotinylated paraoxon to bind to the aptamer has been evaluated by analyzing the surface area of the paraoxon available to the solvent, as well as by calculating the free binding energies. It has been shown that only in the case of aminohexyl immobilized paraoxon can contact the aptamer. At the final stage, the synthesis of paraoxon bound to biotin via aminohexyl was carried out.

Recent Progress in Machine Learning-based Prediction of Peptide Activity for Drug Discovery

2019 ◽  
Vol 19 (1) ◽  
pp. 4-16 ◽  
Author(s):  
Qihui Wu ◽  
Hanzhong Ke ◽  
Dongli Li ◽  
Qi Wang ◽  
Jiansong Fang ◽  
...  
Keyword(s):  
Machine Learning ◽  
Drug Discovery ◽  
Large Scale ◽  
Recent Progress ◽  
High Specificity ◽  
Learning Approaches ◽  
Anticancer Peptides ◽  
The Past ◽  
Traditional Approaches ◽  
Large Scale Screening

Over the past decades, peptide as a therapeutic candidate has received increasing attention in drug discovery, especially for antimicrobial peptides (AMPs), anticancer peptides (ACPs) and antiinflammatory peptides (AIPs). It is considered that the peptides can regulate various complex diseases which are previously untouchable. In recent years, the critical problem of antimicrobial resistance drives the pharmaceutical industry to look for new therapeutic agents. Compared to organic small drugs, peptide- based therapy exhibits high specificity and minimal toxicity. Thus, peptides are widely recruited in the design and discovery of new potent drugs. Currently, large-scale screening of peptide activity with traditional approaches is costly, time-consuming and labor-intensive. Hence, in silico methods, mainly machine learning approaches, for their accuracy and effectiveness, have been introduced to predict the peptide activity. In this review, we document the recent progress in machine learning-based prediction of peptides which will be of great benefit to the discovery of potential active AMPs, ACPs and AIPs.

Personalized antibiotic therapy – a rapid high performance liquid chromatography–tandem mass spectrometry method for the quantitation of eight antibiotics and voriconazole for patients in the intensive care unit

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Tony Böhle ◽  
Ulrike Georgi ◽  
Dewi Fôn Hughes ◽  
Oliver Hauser ◽  
Gudrun Stamminger ◽  
...  
Keyword(s):  
Intensive Care ◽  
Antibiotic Therapy ◽  
High Performance ◽  
High Specificity ◽  
Serum Levels ◽  
Turnaround Time ◽  
Target Range ◽  
Therapeutic Drug ◽  
Monitoring Method ◽  
Adjustment Procedure

AbstractObjectivesFor a long time, the therapeutic drug monitoring of anti-infectives (ATDM) was recommended only to avoid the toxic side effects of overdosing. During the last decade, however, this attitude has undergone a significant change. Insufficient antibiotic therapy may promote the occurrence of drug resistance; therefore, the “one-dose-fits-all” principle can no longer be classified as up to date. Patients in intensive care units (ICU), in particular, can benefit from individualized antibiotic therapies.MethodsPresented here is a rapid and sufficient LC-MS/MS based assay for the analysis of eight antibiotics (ampicillin, cefepime, cefotaxime, ceftazidime, cefuroxime, linezolid, meropenem, and piperacillin) applicated by continuous infusion and voriconazole. In addition a dose adjustment procedure for individualized antibiotic therapy has been established.ResultsThe suggested dose adjustments following the initial dosing of 121 patient samples from ICUs, were evaluated over a period of three months. Only a minor percentage of the serum levels were found to be within the target range while overdosing was often observed for β-lactam antibiotics, and linezolid tended to be often underused. The results demonstrate an appreciable potential for β-lactam savings while enabling optimal therapy.ConclusionsThe presented monitoring method provides high specificity and is very robust against various interferences. A fast and straightforward method, the developed routine ensures rapid turnaround time. Its application has been well received by participating ICUs and has led to an expanding number of hospital wards participating in ATDM.

scholarly journals The interaction landscape between transcription factors and the nucleosome

2017 ◽  
Author(s):  
Fangjie Zhu ◽  
Lucas Farnung ◽  
Eevi Kaasinen ◽  
Biswajyoti Sahu ◽  
Yimeng Yin ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Affinity Purification ◽  
Rotational Symmetry ◽  
Free Dna ◽  
Nucleosomal Dna ◽  
Direct Gene ◽  
Systematic Evolution ◽  
Modes Of Interaction ◽  
Exponential Enrichment ◽  
Rich Interaction

Nucleosomes cover most of the genome and are thought to be displaced by transcription factors (TFs) in regions that direct gene expression. However, the modes of interaction between TFs and nucleosomal DNA remain largely unknown. Here, we use nucleosome consecutive affinity-purification systematic evolution of ligands by exponential enrichment (NCAP-SELEX) to systematically explore interactions between the nucleosome and 220 TFs representing diverse structural families. Consistently with earlier observations, we find that the vast majority of TFs have less access to nucleosomal DNA than to free DNA. The motifs recovered from TFs bound to nucleosomal and free DNA are generally similar; however, steric hindrance and scaffolding by the nucleosome result in specific positioning and orientation of the motifs. Many TFs preferentially bind close to the end of nucleosomal DNA, or to periodic positions at its solvent-exposed side. TFs often also bind nucleosomal DNA in a particular orientation, because the nucleosome breaks the local rotational symmetry of DNA. Some TFs also specifically interact with DNA located at the dyad position where only one DNA gyre is wound, whereas other TFs prefer sites spanning two DNA gyres and bind specifically to each of them. Our work reveals striking differences in TF binding to free and nucleosomal DNA, and uncovers a rich interaction landscape between the TFs and the nucleosome.

Pattern recognition of enrichment levels of SELEX-based candidate aptamers for human C-reactive protein

2017 ◽  
Vol 62 (3) ◽  
Author(s):  
Xinliang Yu ◽  
Ruqin Yu ◽  
Xiaohai Yang
Keyword(s):  
Pattern Recognition ◽  
Latent Variables ◽  
Molecular Descriptors ◽  
Principal Component ◽  
Support Vector ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Systematic Evolution ◽  
Model C ◽  
Exponential Enrichment

AbstractSelecting aptamers for human C-reactive protein (CRP) would be of critical importance in predicting the risk for cardiovascular disease. The enrichment level of DNA aptamers is an important parameter for selecting candidate aptamers for further affinity and specificity determination. This paper is the first report on pattern recognition used for CRP aptamer enrichment levels in the systematic evolution of ligands by exponential enrichment (SELEX) process, by applying structure-activity relationship models. After generating 10 rounds of graphene oxide (GO)-SELEX and 1670 molecular descriptors, eight molecular descriptors were selected and five latent variables were then obtained with principal component analysis (PCA), to develop a support vector classification (SVC) model. The SVC model (C=8.1728 and

Differentiating breast cancer molecular subtypes using a DNA aptamer selected against MCF-7 cells

2018 ◽  
Vol 6 (12) ◽  
pp. 3152-3159 ◽  
Author(s):  
Mei Liu ◽  
Tong Yang ◽  
Zhongsi Chen ◽  
Zhifei Wang ◽  
Nongyue He
Keyword(s):  
Breast Cancer ◽  
Molecular Subtypes ◽  
Personalized Therapy ◽  
Dna Aptamer ◽  
Single Stranded Dna ◽  
Systematic Evolution ◽  
Exponential Enrichment ◽  
Mcf 7

Aptamers are single-stranded DNA or RNA oligonucleotides selected by systematic evolution of ligands by exponential enrichment (SELEX), which show great potential in the diagnosis and personalized therapy of cancers, due to their specific advantages over antibodies.

scholarly journals A Review of Deep Learning Methods for Antibodies

Antibodies ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 12 ◽  
Author(s):  
Jordan Graves ◽  
Jacob Byerly ◽  
Eduardo Priego ◽  
Naren Makkapati ◽  
S. Vince Parish ◽  
...  
Keyword(s):  
Computer Vision ◽  
Deep Learning ◽  
Drug Discovery ◽  
Small Molecules ◽  
Language Processing ◽  
Protein Design ◽  
Therapeutic Drug ◽  
Major Goal ◽  
Antibody Design ◽  
Antibody Drug

Driven by its successes across domains such as computer vision and natural language processing, deep learning has recently entered the field of biology by aiding in cellular image classification, finding genomic connections, and advancing drug discovery. In drug discovery and protein engineering, a major goal is to design a molecule that will perform a useful function as a therapeutic drug. Typically, the focus has been on small molecules, but new approaches have been developed to apply these same principles of deep learning to biologics, such as antibodies. Here we give a brief background of deep learning as it applies to antibody drug development, and an in-depth explanation of several deep learning algorithms that have been proposed to solve aspects of both protein design in general, and antibody design in particular.

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