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Molecules (Basel, Switzerland) Dec 2022The hemostasis system is a complex structure that includes the fibrinolysis system, and Yes this is correct coagulation and anticoagulation parts. Due to the... (Review)
Review
The hemostasis system is a complex structure that includes the fibrinolysis system, and Yes this is correct coagulation and anticoagulation parts. Due to the multicomponent nature, it becomes relevant to study the key changes in the functioning of signaling pathways, and develop new diagnostic methods and modern drugs with high selectivity. One of the ways to solve this problem is the development of molecular recognition elements capable of blocking one of the hemostasis systems and/or activating another. Aptamers can serve as ligands for targeting specific clinical needs, promising anticoagulants with minor side effects and significant biological activity. Aptamers with several clotting factors and platelet proteins are used for the treatment of thrombosis. This review is focused on the aptamers used for the correction of the hemostasis system, and their structural and functional features. G-rich nucleic acid aptamers, mostly versatile G-quadruplexes, recognize different components of the hemostasis system and are capable of correcting the functioning.
Topics: Aptamers, Nucleotide; Hemostasis; Blood Coagulation; G-Quadruplexes; Anticoagulants; Blood Platelets
PubMed: 36500686
DOI: 10.3390/molecules27238593 -
The Analyst Mar 2016Nucleic acid aptamers are promising alternatives to antibodies in analytics. They are generally obtained through an iterative SELEX protocol that enriches a population... (Review)
Review
Nucleic acid aptamers are promising alternatives to antibodies in analytics. They are generally obtained through an iterative SELEX protocol that enriches a population of synthetic oligonucleotides to a subset that can recognize the chosen target molecule specifically and avidly. A wide range of targets is recognized by aptamers. Once identified and optimized for performance, aptamers can be reproducibly synthesized and offer other key features, like small size, low cost, sensitivity, specificity, rapid response, stability, and reusability. This makes them excellent options for sensory units in a variety of analytical platforms including those with electrochemical, optical, and mass sensitive transduction detection. Many novel sensing strategies have been developed by rational design to take advantage of the tendency of aptamers to undergo conformational changes upon target/analyte binding and employing the principles of base complementarity that can drive the nucleic acid structure. Despite their many advantages over antibodies, surprisingly few aptamers have yet been integrated into commercially available analytical devices. In this review, we discuss how to select and engineer aptamers for their identified application(s), some of the challenges faced in developing aptamers for analytics and many examples of their reported successful performance as sensors in a variety of analytical platforms.
Topics: Aptamers, Nucleotide; Biosensing Techniques; Genetic Engineering; Humans; SELEX Aptamer Technique
PubMed: 26864075
DOI: 10.1039/c5an01824b -
Advanced Drug Delivery Reviews Sep 2018Aptamers are single-stranded DNA or RNA molecules capable of tightly binding to specific targets. These functional nucleic acids are obtained by an in vitro Darwinian... (Review)
Review
Aptamers are single-stranded DNA or RNA molecules capable of tightly binding to specific targets. These functional nucleic acids are obtained by an in vitro Darwinian evolution method coined SELEX (Systematic Evolution of Ligands by EXponential enrichment). Compared to their proteinaceous counterparts, aptamers offer a number of advantages including a low immunogenicity, a relative ease of large-scale synthesis at affordable costs with little or no batch-to-batch variation, physical stability, and facile chemical modification. These alluring properties have propelled aptamers into the forefront of numerous practical applications such as the development of therapeutic and diagnostic agents as well as the construction of biosensing platforms. However, commercial success of aptamers still proceeds at a weak pace. The main factors responsible for this delay are the susceptibility of aptamers to degradation by nucleases, their rapid renal filtration, suboptimal thermal stability, and the lack of functional group diversity. Here, we describe the different chemical methods available to mitigate these shortcomings. Particularly, we describe the chemical post-SELEX processing of aptamers to include functional groups as well as the inclusion of modified nucleoside triphosphates into the SELEX protocol. These methods will be illustrated with successful examples of chemically modified aptamers used as drug delivery systems, in therapeutic applications, and as biosensing devices.
Topics: Aptamers, Nucleotide; Humans; Ligands
PubMed: 29626546
DOI: 10.1016/j.addr.2018.04.007 -
Methods (San Diego, Calif.) Mar 2016
Topics: Aptamers, Nucleotide; Biosensing Techniques; SELEX Aptamer Technique
PubMed: 26973146
DOI: 10.1016/j.ymeth.2016.02.015 -
Chemical Reviews Nov 2023Serving as the basis of cell life, interactions between nucleic acids and proteins play essential roles in fundamental cellular processes. Aptamers are unique... (Review)
Review
Serving as the basis of cell life, interactions between nucleic acids and proteins play essential roles in fundamental cellular processes. Aptamers are unique single-stranded oligonucleotides generated by in vitro evolution methods, possessing the ability to interact with proteins specifically. Altering the structure of aptamers will largely modulate their interactions with proteins and further affect related cellular behaviors. Recently, with the in-depth research of aptamer-protein interactions, the analytical assays based on their interactions have been widely developed and become a powerful tool for biomolecular detection. There are some insightful reviews on aptamers applied in protein detection, while few systematic discussions are from the perspective of regulating aptamer-protein interactions. Herein, we comprehensively introduce the methods for regulating aptamer-protein interactions and elaborate on the detection techniques for analyzing aptamer-protein interactions. Additionally, this review provides a broad summary of analytical assays based on the regulation of aptamer-protein interactions for detecting biomolecules. Finally, we present our perspectives regarding the opportunities and challenges of analytical assays for biological analysis, aiming to provide guidance for disease mechanism research and drug discovery.
Topics: Aptamers, Nucleotide; Proteins; Nucleic Acids; SELEX Aptamer Technique
PubMed: 37931070
DOI: 10.1021/acs.chemrev.3c00377 -
Advanced Drug Delivery Reviews Sep 2018
Topics: Aptamers, Nucleotide; Drug Delivery Systems; Humans; Ligands; Molecular Imaging
PubMed: 30442313
DOI: 10.1016/j.addr.2018.11.001 -
Advanced Drug Delivery Reviews Sep 2018The structural flexibility and small size of aptamers enable precise recognition of cellular elements for imaging and therapeutic applications. The process by which... (Review)
Review
The structural flexibility and small size of aptamers enable precise recognition of cellular elements for imaging and therapeutic applications. The process by which aptamers are taken into cells depends on their targets but is typically clathrin-mediated endocytosis or macropinocytosis. After internalization, most aptamers are transported to endosomes, lysosomes, endoplasmic reticulum, Golgi apparatus, and occasionally mitochondria and autophagosomes. Intracellular aptamers, or "intramers," have versatile functions ranging from intracellular RNA imaging, gene regulation, and therapeutics to allosteric modulation, which we discuss in this review. Immune responses to therapeutic aptamers and the effects of G-quadruplex structure on aptamer function are also discussed.
Topics: Aptamers, Nucleotide; Drug Evaluation, Preclinical; Fluorescence Resonance Energy Transfer; Humans; Optical Imaging; Transcription Factors
PubMed: 29981799
DOI: 10.1016/j.addr.2018.07.003 -
Annual Review of Pharmacology and... Jan 2019Oligonucleotides (ONs) can interfere with biomolecules representing the entire extended central dogma. Antisense gapmer, steric block, splice-switching ONs, and short... (Review)
Review
Oligonucleotides (ONs) can interfere with biomolecules representing the entire extended central dogma. Antisense gapmer, steric block, splice-switching ONs, and short interfering RNA drugs have been successfully developed. Moreover, antagomirs (antimicroRNAs), microRNA mimics, aptamers, DNA decoys, DNAzymes, synthetic guide strands for CRISPR/Cas, and innate immunity-stimulating ONs are all in clinical trials. DNA-targeting, triplex-forming ONs and strand-invading ONs have made their mark on drug development research, but not yet as medicines. Both design and synthetic nucleic acid chemistry are crucial for achieving biologically active ONs. The dominating modifications are phosphorothioate linkages, base methylation, and numerous 2'-substitutions in the furanose ring, such as 2'-fluoro, O-methyl, or methoxyethyl. Locked nucleic acid and constrained ethyl, a related variant, are bridged forms where the 2'-oxygen connects to the 4'-carbon in the sugar. Phosphorodiamidate morpholino oligomers, carrying a modified heterocyclic backbone ring, have also been commercialized. Delivery remains a major obstacle, but systemic administration and intrathecal infusion are used for treatment of the liver and brain, respectively.
Topics: Clinical Trials as Topic; Humans; Morpholinos; Nucleic Acids; Oligonucleotides; Oligonucleotides, Antisense
PubMed: 30285540
DOI: 10.1146/annurev-pharmtox-010818-021050 -
Sheng Wu Gong Cheng Xue Bao = Chinese... May 2018Oligonucleotides are widely used as effective tools to regulate gene expression and drugs for targeted gene therapy. Therefore, they are potentially useful for the... (Review)
Review
Oligonucleotides are widely used as effective tools to regulate gene expression and drugs for targeted gene therapy. Therefore, they are potentially useful for the treatment of viral, tumor and hereditary diseases. Therapeutic oligonucleotides include antisense oligonucleotide, small interference RNA (siRNA), Ribozyme, DNAzyme, anti-gene, CpG, decoy and aptamer. Therapeutic oligonucleotides usually carry certain modifications, such as phosphorothioates, fluoro or locked nucleic acids, to enhance the stability and specificity, and reduce the side-effects, because natural oligonucleotides have poor stability in vivo, low specificity and side effects. Now oligonucleotides are usually manufactured by chemical synthesis, with low purity and high cost. Here, we review a novel thermocyclic reaction for the amplification of oligonucleotides, referred to as Polymerase-endonuclease Amplification Reaction (PEAR) catalyzed by two thermostable enzymes. PEAR is simple, efficient, and stable. Comparing with traditional chemical synthesis, PEAR-based enzymatic production of oligonucleotides could be a robust alternative method for the large-scale production of therapeutic or non-therapeutic oligonucleotides.
Topics: Aptamers, Nucleotide; DNA, Catalytic; Genetic Therapy; Nucleic Acid Amplification Techniques; Oligonucleotides; Oligonucleotides, Antisense; RNA, Catalytic; RNA, Small Interfering
PubMed: 29893074
DOI: 10.13345/j.cjb.170401 -
Advanced Drug Delivery Reviews Sep 2018Nucleic acid therapeutics, including siRNAs, miRNAs/antimiRs, gRNAs and ASO, represent innovative and highly promising molecules for the safe treatment of a wide range... (Review)
Review
Nucleic acid therapeutics, including siRNAs, miRNAs/antimiRs, gRNAs and ASO, represent innovative and highly promising molecules for the safe treatment of a wide range of pathologies. The efficiency of systemic treatments is impeded by 1) the need to overcome physical and functional barriers in the organism, and 2) to accumulate in the intracellular active site at therapeutic concentrations. Although oligonucleotides either as modified naked molecules or complexed with delivery carriers have revealed to be effectively delivered to the affected target cells, this is restricted to topic treatments or to a few highly vascularized tissues. Therefore, the development of effective strategies for therapeutic nucleic acid selective delivery to target tissues is of primary importance in order to reduce the occurrence of undesired effects on non-target healthy tissues and to permit their translation to clinic. Due to their high affinity for specific ligands, high tissue penetration and chemical flexibility, short single-stranded nucleic acid aptamers are emerging as very attractive carriers for various therapeutic oligonucleotides. Yet, different aptamer-based bioconjugates, able to provide accumulation into target tissues, as well as efficient processing of therapeutic oligonucleotides, have been developed. In this respect, nucleic acid aptamer-mediated delivery strategies represent a powerful approach able to increase the therapeutic efficacy also highly reducing the overall toxicity. In this review, we will summarize recent progress in the field and discuss achieved objectives and optimization of aptamers as delivery carriers of short oligonucleotides.
Topics: Aptamers, Nucleotide; Drug Carriers; Drug Delivery Systems; Humans; Oligonucleotides
PubMed: 29630917
DOI: 10.1016/j.addr.2018.04.006