Aptamers as inhibitors of target proteins

Missailidis, Sotiris; Hardy, Alison

doi:10.1517/13543770903042337

Cited by 50 publications

(34 citation statements)

References 21 publications

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“…This has led to multiple cases of stable disease and one near complete response in a patient with renal cancer. In addition these promising signs were observed with no significant adverse effects [16,17]. Aptamers that are currently in pre-clinical stages include a chemosensitizer for the treatment of cancer and retinopathy (ARC-127), an inhibitor of the isoform b of transcription factor HMGA1 (NOX-A50), and the anti-MUC1 aptamer designed against the Muc-1 protein in epithelial malignant cells [17].…”

Section: Cancermentioning

confidence: 98%

“…However, these benefits become disadvantages when considering their use as in vivo therapeutic agents, due to their inherent instability. It is possible to improve their halflife through the use of base modifications and the linkage of polyethylene glycol (PEG) [17]. Base modifications, including 2'-O-methyl pyrimidines, 2'-deoxy purines, and 2'-fluorine-pyrimidines, have been shown to extend their in vivo stability to 86 hours [18].…”

Section: Aptamers As Therapeutics and Therano-sticsmentioning

confidence: 99%

“…In most cases, the actual binding of the aptamer to the target inhibits its biological activity, with this being due to interference with the enzymatic catalytic site, or ligand receptor recognition sites, or possibly inducing allosteric effects, such as conformational changes resulting in loss of function, or through interaction with its natural ligand [17,18]. Due to loss of function, aptamers have found a niche in virtually every area of pathology, including vaccine production [21,22], virology [23], parasitology [24,25], and oncology [26,27].…”

Section: Aptamers As Therapeutics and Therano-sticsmentioning

confidence: 99%

See 2 more Smart Citations

Aptamer Therapeutics: The 21st Century`s Magic Bullet of Nanomedicine

Shigdar¹,

Luczo²,

Wei³

et al. 2010

TOPROCJ

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Aptamers, also known as chemical antibodies, are short single-stranded DNA, RNA or peptide molecules. These molecules can fold into complex three-dimensional structures and bind to target molecules with high affinity and specificity. The nucleic acid aptamers are selected from combinatorial libraries by an iterative in vitro selection procedure known as systematic evolution of ligands by exponential enrichment (SELEX). As a new class of therapeutics and drug targeting entities, bivalent and multivalent aptamer-based molecules are emerging as highly attractive alternatives to monoclonal antibodies as targeted therapeutics.Aptamers have several advantages, offering the possibility of overcoming limitations of antibodies: 1) they can be selected against toxic or non-immunogenic targets; 2) aptamers can be chemically modified by using modified nucleotides to enhance their stability in biological fluids or via incorporating reporter molecules, radioisotopes and functional groups for their detection and immobilization; 3) they have very low immunogenicity; 4) they display high stability at room temperature, in extreme pH, or solvent; 5) once selected, they can be chemically synthesized free from cell-culturederived contaminants, and they can be manufactured at any time, in large amounts, at relatively low cost and reproducibly; 6) they are smaller and thus can diffuse more rapidly into tissues and organs, leading to faster targeting in drug delivery; 7) they have lower molecular weight that can lead to faster body clearance, resulting in a low background noise for imaging and minimizing the radiation dose to the patient in diagnostic imaging. Thus, the high selectivity and sensitivity, ease of screening and production, chemical versatility as well as stability make aptamers a class of highly attractive agents for the development of novel therapeutics, targeted drug delivery vehicles and molecular imaging.In the review, we will discuss the latest technological advances in developing aptamers, its application as a novel class of drug on its own, as well as in surface functionalization of both polymer nanoparticles or nanoliposomes in the treatment of cancer, viral and autoimmune diseases.

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Section: Cancermentioning

confidence: 98%

Section: Aptamers As Therapeutics and Therano-sticsmentioning

confidence: 99%

Section: Aptamers As Therapeutics and Therano-sticsmentioning

confidence: 99%

See 1 more Smart Citation

Aptamer Therapeutics: The 21st Century`s Magic Bullet of Nanomedicine

Shigdar¹,

Luczo²,

Wei³

et al. 2010

TOPROCJ

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show abstract

“…104 Aptamers have been demonstrated to have more specific and higher affinity for the intended target than other ligands (eg, antibodies). 105 Cheng et al reported DTX-encapsulated NPs formulated with PLGA-b-PEG copolymer and surface functionalized with the A10 RNA aptamers that recognize the extracellular domain of the prostate-specific membrane antigen, a well characterized antigen expressed on the surface of prostate cancer cells. 106 L Gao et al co-assembled thrombin aptamer and DTX on mesoporous silica NPs against tumor-cell proliferation.…”

Section: Aptamersmentioning

confidence: 99%

How nanotechnology can enhance docetaxel therapy

Zhang¹,

Zhang²

2013

IJN

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Docetaxel has been recognized as one of the most efficient anticancer drugs over the past decade; however, its poor water solubility and systemic toxicity have greatly limited its clinical application. In recent decades, the emergence of nanotechnology has provided new drug delivery systems for docetaxel, which can improve its water solubility, minimize the side effects and increase the tumor-targeting distribution by passive or active targeting. This review focuses on the research progress in nanoformulations related to docetaxel delivery -such as polymer-based, lipid-based, and lipid-polymer hybrid nanocarriers, as well as inorganic nanoparticles -addressing their structures, characteristics, preparation, physicochemical properties, methods by which drugs are loaded into them, and their in vitro and in vivo efficacies. Further, the targeted ligands used in the docetaxel nanoformulations, such as monoclonal antibodies, peptides, folic acid, transferrin, aptamers and hyaluronic acid, are described. The issues to overcome before docetaxel nanoformulations can be used in clinical and commercial applications are also discussed.

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“…Owing to the high specific affinity of an aptamer to its target, it is thought to resemble chemical antibodies, with the dissociation constants ranging from the nanomolar to picomolar level (Iliuk, Hu, and Tao 2011). Since then, people have begun to study how to utilize the advantages of aptamers, and the applications of aptamers remains dynamic in such fields as disease diagnosis (Nimjee, Rusconi, and Sullenger 2005;Gubala et al 2012;Liu et al 2009), drug screening (Missailidis and Hardy 2009), bioseparation and bioanalysis applications (de-los-Santos-Á lvarez et al 2008;Mairal et al 2008;Smith et al 2007), and even RNA computing (Shapiro and Gil 2008). Furthermore, the binding system of aptamer-target will be destructed when some negative conditions were introduced, such as high-temperature or denaturing agents.…”

Section: Introductionmentioning

confidence: 99%

Rapid and Efficient Proteolysis for Protein Analysis by an Aptamer-Based Immobilized Chymotrypsin Microreactor

Xiao

Man

et al. 2013

Analytical Letters

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Efficient protein digestion is a key step for successful mass spectrometry identification. However, traditional in-solution digestion suffers some drawbacks, such as autolysis of protease, long analysis times and lack of control. Recently, specific single-stranded nucleic acids, aptamers, screened from random sequence pools, have been performed high affinity for targets. In this paper, we have developed a novel enzyme reactor, which immobilized chymotrypsin based on aptamer-grafted silica beads. Mixed proteins, which consist of bovine serum albumin, myoglobin, and cytochrome c, were used as samples, to evaluate the digestion performance of the enzymatic reactor. With the use of this novel tool, proteins were digested in 40 min to an extent similar to that achieved with soluble enzyme at 37 C after 16 h. Moreover, enzymatic reactor regeneration was carried out through chymotrypsin elution and re-immobilization. The advanced characteristics of the aptamer-based chymotrypsin reactor demonstrated that aptamers could serve as novel materials for rapid and efficient enzyme immobilization and application in protein studies.

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Aptamers as inhibitors of target proteins

Cited by 50 publications

References 21 publications

Aptamer Therapeutics: The 21st Century`s Magic Bullet of Nanomedicine

Aptamer Therapeutics: The 21st Century`s Magic Bullet of Nanomedicine

How nanotechnology can enhance docetaxel therapy

Rapid and Efficient Proteolysis for Protein Analysis by an Aptamer-Based Immobilized Chymotrypsin Microreactor

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