Aptamers—basic research, drug development, and clinical applications

Proske, Daniela; Blank, Michael; Buhmann, Raymund; Resch, Ansgar

doi:10.1007/s00253-005-0193-5

Cited by 258 publications

(172 citation statements)

References 64 publications

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“…Furthermore, the increasing focus on the use of aptamers as tools for diagnostics, target validation and drug discovery will maximize the potential of aptamers in therapeutics. 69,70 As for gene therapy, an efficient and targeted mode of delivery continues to be the major roadblock in achieving the full potential of RNA therapeutics as intracellular drugs. Results from a multipronged approach to HIV gene therapy that involves the combined delivery of aptamers, ribozymes and siRNAs to the cell are very promising, but their ultimate utility awaits further clinical evaluation.…”

Section: Prospectsmentioning

confidence: 99%

Gene therapy progress and prospects: RNA aptamers

2007

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Aptamers are oligonucleotides evolved in vitro or in nature to bind target ligands with high affinity and specificity. They are emerging as powerful tools in the fields of therapeutics, drug development, target validation and diagnostics. Aptamers are attractive alternatives to antibody-and small-moleculebased therapeutics owing to their stability, low toxicity, low immunogenicity and improved safety. With the recent approval of the first aptamer drug Macugen by the US FDA, there is great impetus to develop therapeutic aptamers that can target a wide array of disease states. The recent demonstration that aptamer activity can be reversed by the administration of a simple antidote greatly enhances the potential value of aptamers as therapeutic agents.

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Section: Prospectsmentioning

confidence: 99%

Gene therapy progress and prospects: RNA aptamers

2007

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“…Aptamers are short nucleic acid sequences (single-stranded RNA or DNA) that selectively bind with high specificity and affinity to non-nucleic targets such as proteins as well as a large variety of other targets that include ions, toxins, drug molecules, cells and tissues [45][46][47][48] (see ref. 49 for a comprehensive aptamer database). Binding occurs not through sequence hybridization but via interaction of the target with particular 3-D stemloop and internal loop structures formed by the nucleic acids.…”

Section: Iii1 Nucleic Acid Aptamer Microarraysmentioning

confidence: 99%

Microarray methods for protein biomarker detection

Lee

Wark

Corn

2008

Analyst

137

108

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The application of protein biomarkers as an aid for the detection and treatment of diseases has been subject to intensified interest in recent years. The quantitative assaying of protein biomarkers in easily obtainable biological fluids such as serum and urine offers the opportunity to improve patient care via earlier and more accurate diagnoses in a convenient, non-invasive manner as well as providing a potential route towards more individually targeted treatment. Essential to achieving progress in biomarker technology is the ability to screen large numbers of proteins simultaneously in a single experiment with high sensitivity and selectivity. In this article, we highlight recent progress in the use of microarrays for high-throughput biomarker profiling and discuss some of the challenges associated with these efforts. I IntroductionThe discovery of protein biomarkers whose change in expression level or state correlates with the progression of a disease is becoming increasingly important. Once validated, proposed biomarkers can be involved in achieving an earlier diagnosis, differentiating between disease types with greater accuracy, and assessing response to treatment. Prominent examples of biomarkers include proteins that are associated with a variety of cancers, 1-4 as well as heart, 5,6 renal, 7,8 andAlzheimer's 9,10 diseases.Most biomarker studies reported to date have focused on serum-, plasmaand urine-based samples. A number of other possibilities include saliva, tears, breath condensates, cerebrospinal fluid and tissue lysates extracted from biopsy samples. There are several excellent reviews detailing biomarker discovery and validation. [11][12][13][14][15] The potential benefits of biomarkers have greatly motivated both academic and industry researchers to apply new proteomic technologies for biomarker discovery and to develop quantitative analytical methodologies for rapid and sensitive biomarker detection. Many clinically relevant biomarkers reside in blood at picomolar concentrations and lower, which is five to seven orders of magnitude lower than the most abundant plasma proteins. Therefore, protein detection with high specificity and sensitivity is required; unfortunately, no universal ultrasensitive enzymatic amplification method (such as PCR for the case of nucleic acid detection) exists for proteins. Additionally, it is desirable to screen multiple proteins simultaneously in a single sample. Multiplexed measurements are attractive not only for economic reasons but also for identifying characteristic signal patterns associated with the relative changes in entire sets of proteins as this will provide much more insight and diagnostic accuracy than individual biomarker measurements.hyejinlee@knu.ac.kr. 14,19,[24][25][26][27][28][29][30] Although microarray methods are wellestablished for high-throughput nucleic acid studies, their application for protein detection has been limited by issues such as the surface immobilization of protein capture probes without loss in bioactivity as well a...

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“…Nucleic acid aptamers are oligonucleotides which fold into 3D structures that bind with high specificity and high affinity to target molecules. 45,46 Anchored DNA aptamers could have applications in areas such as ligand-targeted drug delivery systems [47][48][49][50][51] or molecular detection assays. Structural heterogeneity can offer added functionality to engineered materials.…”

Section: Introductionmentioning

confidence: 99%

Partitioning of Membrane-Anchored DNA between Coexisting Lipid Phases

Beales

Vanderlick

2009

J. Phys. Chem. B

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The partitioning of different cholesterol-modified single-stranded DNA molecules (chol-DNAs) between the domains of phase-separated lipid vesicles is investigated by laser-scanning confocal fluorescence microscopy. All chol-DNAs studied preferentially localized into the fluid phase of giant vesicles in liquid-solid phase coexistence (1:1 DLPC:DPPC, 1:1 DLPC:DMPE). Partitioning behavior of chol-DNAs into liquid-liquid phase-separated vesicles (DOPC/DPPC/cholesterol) was found to be less straightforward. Single-cholesterolanchored DNA molecules partitioned roughly equally between coexisting domains, whereas chol-DNAs with two cholesterol anchors were seen to be enriched in the liquid-ordered domains with apparent surface concentrations up to double that of the liquid-disordered phase. Quantitative analysis of the fluorescence intensity of DNA between the two phases also revealed a weaker dependence of the apparent partitioning on the initial lipid composition of the vesicles. We rationalize these observations by proposing a simple partitioning model based on the conformational entropy of insertion of a cholesterol anchor into each phase.

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Aptamers—basic research, drug development, and clinical applications

Cited by 258 publications

References 64 publications

Gene therapy progress and prospects: RNA aptamers

Gene therapy progress and prospects: RNA aptamers

Microarray methods for protein biomarker detection

Partitioning of Membrane-Anchored DNA between Coexisting Lipid Phases

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