The Aptamer Handbook: Functional Oligonucleotides and Their Applications

Highly specific aptamers for analytics and therapeutics
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This first overview in the field is of prime interest for a broad audience of scientists both in academia and in industry who wish to expand their knowledge on the potential of new oligonucleotide functions and their applications. Read more Read less. Amazon Global Store US International products have separate terms, are sold from abroad and may differ from local products, including fit, age ratings, and language of product, labeling or instructions.

Manufacturer warranty may not apply Learn more about Amazon Global Store. Review "Considering the overall effort by the editor to gather work by some of the leading researchers on aptamers, I believe The Aptamer Handbook will be referred to as an encyclopedia on aptamer research. See all Product description. No customer reviews. Share your thoughts with other customers.

Write a customer review. Most helpful customer reviews on Amazon. November 5, - Published on Amazon. This is a great general knowledge book for anyone wanting to perform an Aptamer Selection, however, as you may know Pair it with some good literature searching on Pubmed. Go to Amazon. Discover the best of shopping and entertainment with Amazon Prime. Since aptamers can be selected for specific binding to small molecules, they are applicable for detecting small molecule ligands, such as cellular metabolites, or can be used for therapeutic drug monitoring.

Because of their outstanding properties, aptamers are used in combination with nanoparticles for biomedical sensing and detection, and as aptamer-nanoparticle conjugates for smart drug delivery. The aptamer-nanoparticle conjugates enable active controlled delivery of drugs that are incorporated in the nanoparticles once they are bound to a disease site because of the aptamer affinity to this site [5]. This research area has already seen substantial growth in recent years [24].

We will exemplify here results in the development of aptamer-based nanomaterials for cancer detection and imaging. In this special field, the progress has been remarkable. For exact selection of the proper treatment for cancer, shorter detection and diagnosis timelines are essential. Therefore, the development of quick and easy detection methods to determine the different cancer types is required. Much more than for other diseases, in cancer the consistent multitude of different cancer cells need the implementation of personalised treatment.

Molecular recognition of disease-specific biomarkers, especially the recognition of proteins or other biological molecules that differentiate between normal and abnormal cells is a fundamental challenge in cancer cell biology [25].

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Aptamers are very suitable for this purpose. Systematic in-vitro development provides aptamers that are able to detect even small differences between molecules and between various cell types. Aptamers have a low molecular weight, fast tissue penetration and low toxicity. They can be specifically labelled with various reporters for molecular recognition. Up to now, many of the published aptamer-nanoparticle assays or sensors for cancer detection are based on a handful of aptamers that are specific for T-cell leukaemia and B-cell lymphoma.

This panel of DNA aptamers was selected directly from cancer cells by Cell-SELEX [26] for the recognition of molecular differences among leukaemia patient samples [27]. All of the aptamers show high specificity for their respective target cells and equilibrium dissociation constants in the nanomolar to subnanomolar range. Gold nanoparticles have been modified with these aptamers for use as targeted probes for imaging and studying lymphoma or leukaemia cancer cells [31—33]. One especially user-friendly application, which enables cancer detection very easily and in the shortest time with a strip-based assay [34], is worth spotlighting.

When the sample solution containing Ramos cells was applied to the sample pad, the solution migrated by capillary action past the conjugate pad and then rehydrated the aptamer conjugated gold nanoparticles. The Ramos cells interacted first with the modified nanoparticles and then continued migrating along the strip.

2018 -12 13 Webinar: Oligo pools design, synthesis, and research applications

When reaching the test zone, they were captured by a second reaction between the Ramos cells and the immobilised biotinylated aptamers. This is visualised as a characteristic red band due to the accumulation of gold nanoparticles in the test zone. Under optimal conditions, the test strip was capable of detecting a minimum of 4, Ramos cells by visual judgment only, without instrumentation. If a portable strip reader was used, a minimum of cells were detectable.

The measurements in buffer solution could be made within 15 minutes. The feasibility of the test system for the detection of cancer cells in biological fluids was evaluated and a successful determination of Ramos cells in human blood could be shown. Chen et al. The authors firstly tuned the FRET-mediated emission signature by changing the doping ratio of three different dyes such that the nanoparticles would exhibit multiple colours upon excitation with a single wavelength.

Fluorescent imaging fig. Previously, Herr et al. Beside the use of the above-mentioned DNA aptamers for leukaemia cells, a few nanoparticle-based cancer detection assays have been described. For example, Lu et al. They used oval-shaped gold nanoparticles, which they conjugated with a monoclonal antibody for human epidermal growth factor receptor and breast cancer specific RNA aptamers.

These aptamers are the first reported RNA aptamers selected to bind a tumour-associated membrane antigen and the first application of RNA aptamers to a prostate cancer specific cell marker. The set of aptamers is very specific and even able to discriminate different human prostate cancer cell lines.

The dissociation constants of the PSMA aptamers are in a low nanomolar range. Walter et al. MUC1 is a glycoprotein expressed on most epithelial cell surfaces and present in a variety of malignant tumours. The selected aptamers were shown to detect MCF-7 breast cancer cells. Cheng et al.

The sensor was based on a construct of three specially designed DNA strands quencher, quantum dot-labelled reporter and the MUC1 aptamer stem , which allowed a strong fluorescence in the absence of the analyte. In the presence of MUC1 peptides, the fluorescence intensity decreased as a result of the structure switch of the aptamer strand when binding MUC1.

In this way, the quencher and fluorescence reporter were brought into close proximity, which led to the occurrence of fluorescence resonance energy transfer, FRET, between the quencher and quantum dot. The detection limit for MUC1 with this approach was at the nanomolar level, and a linear response could be established for the approximate range found in blood serum.

The method offers the possibility of improvement in the early diagnosis of different types of epithelial cancers. AS is being administered systemically in clinical trials. This aptamer is a member of a novel class of antiproliferative agents known as G-rich oligonucleotides GROs. These are non-antisense, guanosine-rich phosphodiester oligodeoxynucleotides that form stable G-quadruplex structures. The biological activity of GROs results from their binding to specific cellular proteins. One important target protein of GROs has been previously identified as nucleolin, a multifunctional protein expressed at high levels by cancer cells [43].

Ko et al. The so-called fluorescence derby imaging used dual colour quantum dots conjugated by the AS aptamer targeting nucleolin on one hand and the arginine-glycine-aspartic acid targeting the integrin alpha v beta 3 on the other. The simultaneous fluorescence imaging of the cellular distribution of nucleolin and integrin using quantum dots enabled easy monitoring of separate targets in cancer cells and in normal healthy cells.

These results suggest the feasibility of concurrent visualisation of quantum dot-based multiple cancer biomarkers using small molecules such as aptamer or peptide ligands. Hua et al. The MUC1 aptamer was covalently conjugated to magnetic beads to capture breast cancer cells through affinity interaction between the aptamer and MUC1 protein. The MUC1 protein is overexpressed on the cancer cell surface. The captured cells were detected by a specially constructed nano-bio-probe consisting of the nucleolin aptamer AS and quantum dots.

The quantum dots were homogeneously coated on the surfaces of monodispersed silica nanoparticles. The nano-bio-probe attached to the surface of the pathogenic cells through the affinity of the AS aptamer to nucleolin, which is also overexpressed in MCF-7 breast cancer cells. Simultaneous usage of the two aptamers as recognition elements improved selectivity. Aptamers combined with nanoparticles hold great potential for effective detection of cancer even in the early stages of the disease.

However, there are only a few aptamers available for different types of cancer cells currently. By development of further aptamers specific for cancer cells and markers, it will be possible to expand this field enormously. Aptamers were first introduced as imaging probes for in-vivo studies in , when Charlton et al. This aptamer showed a higher signal-to-background ratio than its antibody counterpart, demonstrating the potential applications of aptamers as imaging probes for in-vivo studies.

Taking advantage of rapidly expanding nanobiotechnology-based developments, aptamer-nanoparticle conjugation forms the basis of a new chemical and biological strategy for in-vivo imaging. Because of their small size, nanoparticles can interact readily with biomolecules both on the surface and the cells. When conjugated with biomolecular affinity ligands, such as aptamers, they are considered to be a revolutionary approach for detection of various diseases that can be combined with directed therapy strategies. Targeted metallic nanoparticles modified with aptamers as targeting agents have shown potential as a platform for development of molecular-specific contrast agents.

Javier et al. The group devised a novel conjugation approach with an extended aptamer design where the extension was complementary to an oligonucleotide sequence attached to the surface of the gold nanoparticles. Recently, Kim et al. In this way, a targeted molecular CT imaging system capable of specific imaging of prostate cancer cells that express the PSMA protein was established. To overcome limitations in targeted cell labelling related to molecule size and instability of the detection molecules, Zhou et al.

The hybrid DNA aptamer-dendrimer nanomaterial was used for labelling acute leukaemia cells. The results of binding studies with flow cytometry and fluorescence imaging microscopy showed high binding affinity and specificity of the constructed nanomaterial. Owing to the very small size of the created aptamer-dendrimers, the authors assume a principal applicability as contrast agents for specific in-vivo cancer imaging.

Most of these promising studies have been performed on the basis of in-vitro cell assays. The in-vivo functionality of these novel multifunctional nanoparticles has to be proved by further studies. Nevertheless, in-vivo effects of aptamer-nanoparticles used for cancer visualisation in mouse models have recently been described [50]. The AS aptamer specific to the nucleolin protein was conjugated to cobalt-ferrite nanoparticles surrounded by fluorescent rhodamine within a silica shell and to gallium 67 Ga. These multimodal nanoparticles were administered by intravenous injection into tumour-bearing nude mice and their biodistribution was analysed fig.

The conjugates showed rapid blood clearance and accumulation in the tumour site, detected with scintigraphic images and magnetic resonance imaging. Furthermore, accumulation of the conjugate was corroborated by fluorescence imaging of the tumour after organ extraction. However, the conjugate was also shown to accumulate nonspecifically in liver and intestine, which may be a result of the size of the particles.

Accumulation of nanoparticles in the liver is a widespread phenomenon and a problem independent of aptamers. To circumvent this problem, not only the influence of particle material, charge, and size, but also surface modifications are currently being studied [51]. One can foresee the promise of this technology once particle size can be optimised to minimise nonspecific uptake. Apart from their use as a sensing platform for bioanalysis discussed above, aptamer-nanomaterial conjugates have also been applied in targeted drug delivery when used as carriers bound with cargo molecules, such as drugs or functional proteins.

Cargos can be loaded onto nanoparticles either covalently or noncovalently. Covalent modifications of cargoes are generally achieved through standard gold-thiol chemistry, peptide bond formation or similar methods. For noncovalent introduction of cargo molecules, electrostatic adsorption and hydrophobic interaction schemes are commonly employed.

Regardless of the kind of cargo loading, conjugated nanoparticles are very appropriate for in-vivo applications because of their biocompatibility [52]. In a pioneering nanoparticle-targeting study, they demonstrated that the A aptamer can be used to target poly lactic acid -blockpolyethylene glycol copolymer nanoparticles to PSMA positive prostate cancer cells. The resulting nanomaterial showed a fold increase in binding to PSMA expressing prostate cancer cells in comparison with untargeted nanoparticles [53].

The A aptamer was again used to target modified poly D,L-lactic-co-glycolic acid PLGA nanoparticles to deliver docetaxol to prostate tumours in-vivo, where complete tumour regression was found in five out of seven mice after a single intratumoural injection. Moreover, all of the treated animals survived a day study [54]. In a next step, the group optimised their protocol for production of PEGylated PLGA nanoparticles and conjugated the resulting nanoparticles to the A aptamer and to docetaxel and the related 14 C-paclitaxel.

After systemic administration, the delivery of these nanoparticles conjugates to tumours was enhanced 3. Biodistribution patterns to the heart, lungs and kidneys of the treated mice did not show substantial accumulation of nanoparticles.

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However, the presence of high aptamer surface density led to an increase in nanoparticle accumulation in liver and spleen. This was likely to be due to aptamer masking the PEG layers on the surfaces of the nanoparticles and compromising the nanoconjugates antibiofouling properties in vivo. Thus, in engineering targeted nanoparticles, it is necessary to balance the tumour-targeting ligand surface density and the antibiofouling surface properties [55, 56].

A dosage of 0. Furthermore, the same group demonstrated the feasibility of their systems for multiple drug therapy: targeted dual-drug combination based on nanoparticles with hydrophobic docetaxel and hydrophilic Pt IV drug. Superior efficiency over single-drug nanoparticle analogues or nontargeted nanoparticles could be demonstrated [58].

In an additional study, the anti-PSMA A10 aptamer was conjugated with superparamagnetic iron oxide nanoparticles and with a doxorubicin cargo, with aim of a dual function as combined prostate cancer imaging with magnetic resonance and therapy. The in-vitro cytotoxicity assay showed that the nanoparticle-mediated doxorubicin delivery and the delivery of free doxorubicin are equally potent against PSMA-positive cancer cells.

More importantly, treatment with the aptamer-functionalised nanoparticles killed Aravind et al. These nanoparticles were functionalised with AS antinucleolin aptamers for site-specific targeting against tumour cells that overexpress nucleolin receptors. Cytotoxicity studies were carried out in two different cancer cell lines breast cancer MCF-7 cells and human gliosarcoma GI-1 cells.

Drug-loading studies indicated that with the same drug load, the aptamer-targeted nanoparticles show an enhanced cancer killing effect compared with the corresponding nontargeted nanoparticles. In addition, the lipid-polymer combinational nanoparticles exhibited high encapsulation efficiency and superior sustained drug release than the drug loaded in plain polymer nanoparticles.

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The Aptamer Handbook: Functional Oligonucleotides and Their Applications. Editor(s). Dr. Sven Klussmann. First published February These functions comprise high affinity binding (aptamers), catalytic activity The Aptamer Handbook: Functional Oligonucleotides and Their Applications.

The results of in-vitro imaging of cancer cells [41, 44] indicated that aptamer-conjugated quantum dots have the potential to be useful in imaging and protein expression profiling of living cells and fixed tissue, as well as in-vivo studies and drug delivery, although their use for the latter application may be limited by the relatively high cytotoxicity of quantum dots [61, 62]. However, there are intentions to use this material in vivo.

For example, Savla et al. Doxorubicin was attached to quantum dots via a pH-sensitive hydrazone bond in order to provide stability of the complex in the systemic circulation and drug release in the acidic environment inside cancer cells. In a mouse model with human ovarian cancer xenografts, more MUC1 aptamer quantum dots accumulated in the tumours when compared with nonmodified quantum dots.

Ex-vivo analysis of organs confirmed higher uptake in the tumour and lower uptake in other organs. The data obtained demonstrated the high potential of targeted quantum dot conjugates in the treatment of cancer. Besides other carriers, such as micelles and nanogels, aptamer-based drug delivery via nanoparticles promises to represent a new trend in specific therapeutic applications.

It may contribute to the development of the next generation of nano-scale diagnostic and therapeutic modalities. Austin: Andrew Ellington. On Aptamers; March 6 [cited Dec 20]; [about three screens]. In vitro selection of RNA molecules that bind specific ligands. Adaptive recognition by nucleic acid aptamers. Aptamer-gated nanoparticles for smart drug delivery. High-resolution molecular discrimination by RNA. Biomol Eng.

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Curr Med Chem. Biotechnol Healthc. Medical applications of aptamers. Res Pharm Sci. Aptamer therapeutics advance.

Aptamer-modified nanoparticles and their use in cancer diagnostics and treatment

Curr Opin Chem Biol. Chem Biol. The generation and characterization of antagonist RNA aptamers to human oncostatin M. J Biol Chem. Extending the lifetime of anticoagulant oligodeoxynucleotide aptamers in blood. Nucl Med Biol.