Aptamer therapeutics advance

Lee, Jennifer F.; Stovall, Gwendolyn M.; Ellington, Andrew D.

doi:10.1016/j.cbpa.2006.03.015

Cited by 348 publications

(231 citation statements)

References 71 publications

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“…46,[52][53][54][55] Consequently, the merging of aptamer and microarray technologies to create bioaffinity sensors for the simultaneous detection of multiple protein or biomarker targets from a biological sample is still at a very early stage.…”

Section: Iii1 Nucleic Acid Aptamer Microarraysmentioning

confidence: 99%

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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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Section: Iii1 Nucleic Acid Aptamer Microarraysmentioning

confidence: 99%

“…52,56,[62][63][64][65][66][67][68] This is due to the difficulty in tethering RNA molecules to a surface without loss of functionality. Most initial efforts at RNA microarray fabrication have involved modified RNA sequences such as biotinylated RNA 56,64,65 or thiol-modified RNA.…”

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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“…Aptamers are selected from very large random libraries by a procedure known as SELEX (systematic evolution of ligands by exponential enrichment)-an iterative process of enriching the mixture in molecules with high binding affinity and selectivity against the desired target (18,19). Aptamers themselves are considered promising candidates for many therapeutic applications (20) and have also been used to facilitate targeted uptake of other therapeutic molecules. For example, aptamers directed against prostatespecific membrane antigen have been linked to drug-laden nanoparticles (21), small interfering RNA (22), and a ribosomal toxin (23) to destroy prostate cancer cells.…”

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confidence: 99%

Aptamer-based endocytosis of a lysosomal enzyme

Chen

Dellamaggiore

Ouellette

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

144

120

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Enzyme replacement therapy for lysosomal storage diseases is currently based on endocytosis of lysosomal enzymes via the mannose or mannose 6-phosphate receptors. We are developing a technology for endocytosis of lysosomal enzymes that depends on generic, chemically conjugated reagents. These reagents are aptamers (singlestranded nucleic acid molecules) selected to bind to the extracellular domain of the mouse transferrin receptor. After selection, an RNA aptamer and a DNA aptamer were modified with biotin and linked to dye-labeled streptavidin for detection by confocal microscopy. Aptamer-streptavidin conjugates showed saturable uptake into mouse fibroblasts (Ltk ؊ cells), which could be inhibited by an excess of free aptamer but not by tRNA, calf thymus DNA, or transferrin. The RNA aptamer-streptavidin conjugate was mouse-specific, as human cells (293T) did not take it up unless first transfected with the mouse transferrin receptor. Some streptavidin separated from the recycling pathway of transferrin and colocalized with lysosomes. After characterization in the model system, the DNA aptamer was conjugated to a lysosomal enzyme, ␣-L-iduronidase, from which mannose 6-phosphate had been removed. The aptamer had been modified by attachment of terminal glycerol for oxidation by periodate and reaction of the resulting aldehyde with amino groups on the protein. Dephospho-␣-L-iduronidase-aptamer conjugate was taken up in saturable manner by ␣-L-iduronidase-deficient mouse fibroblasts, with half-maximal uptake estimated as 1.6 nM. Endocytosed enzyme-aptamer conjugate corrected glycosaminoglycan accumulation, indicating that it reached lysosomes and was functional in those organelles. Both uptake and correction were inhibited by unconjugated aptamer, confirming the role of the aptamer in receptor-mediated endocytosis.lysosomal storage disease ͉ transferrin receptor

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“…Aptamers comprise either DNA or RNA and typically have a longer chain length (ie, approximately 40 nucleotides) than other ODN. These agents have a specific 3D structure (Ellington &Szostak 1992;Jayasena 1999) that determines their ability to bind specifically to their protein target acting in a similar manner to conventional antibody therapies (Lee et al 2006). ISS molecules are single stranded, which sequence is enriched with unmethylated cysteine and guanine motifs (CpG) motifs (Vollmer et al 2004).…”

Section: Antisense Oligonucleotides: An Overviewmentioning

confidence: 99%