From SOMAmer-Based Biomarker Discovery to Diagnostic and Clinical Applications: A SOMAmer-Based, Streamlined Multiplex Proteomic Assay

Kräemer, Stephan; Vaught, Jonathan D.; Bock, C.; Gold, Larry; Katilius, Evaldas; Keeney, Tracy R.; Kim, Nancy; Saccomano, Nicholas A.; Wilcox, Sheri K.; Zichi, Dom; Sanders, Glenn M.

doi:10.1371/journal.pone.0026332

Cited by 249 publications

(226 citation statements)

References 12 publications

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“…However, we do not know whether or not this binding is specific to cancer cells (that is, transformed cell lines that have been immortalized in culture); we have not done a control with breast cells that have not been immortalized. This is, of course, just one of many efforts to improve the performance of SELEX by altering the matrix upon which selection operates, as noted in the introduction (11)(12)(13)(14)(15)(16)(17). Accordingly, it is important to note the differences between what we have done here and what is being done in other laboratories.…”

Section: Discussionmentioning

confidence: 94%

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In vitro selection with artificial expanded genetic information systems

Sefah

Yang

Bradley

et al. 2013

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

291

250

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Artificially expanded genetic information systems (AEGISs) are unnatural forms of DNA that increase the number of independently replicating nucleotide building blocks. To do this, AEGIS pairs are joined by different arrangements of hydrogen bond donor and acceptor groups, all while retaining their Watson-Crick geometries. We report here a unique case where AEGIS DNA has been used to execute a systematic evolution of ligands by exponential enrichment (SELEX) experiment. This AEGIS-SELEX was designed to create AEGIS oligonucleotides that bind to a line of breast cancer cells. AEGIS-SELEX delivered an AEGIS aptamer (ZAP-2012) built from six different kinds of nucleotides (the standard G, A, C, and T, and the AEGIS nonstandard P and Z nucleotides, the last having a nitro functionality not found in standard DNA). ZAP-2012 has a dissociation constant of 30 nM against these cells. The affinity is diminished or lost when Z or P (or both) is replaced by standard nucleotides and compares well with affinities of standard GACT aptamers selected against cell lines using standard SELEX. The success of AEGIS-SELEX relies on various innovations, including (i) the ability to synthesize GACTZP libraries, (ii) polymerases that PCR amplify GACTZP DNA with little loss of the AEGIS nonstandard nucleotides, and (iii) technologies to deep sequence GACTZP DNA survivors. These results take the next step toward expanding the power and utility of SELEX and offer an AEGIS-SELEX that could possibly generate receptors, ligands, and catalysts having sequence diversities nearer to that displayed by proteins.

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Section: Discussionmentioning

confidence: 94%

“…Following a slightly different rationale, SomaLogic has obtained slow off-rate modified aptamers (SOMAmers) by appending hydrophobic side chains (e.g., benzyl, naphthyl, tryptamino, and isobutyl) to nucleobases (15). In one set of SOMAmers targeted against ∼800 different human proteins, affinities in the 0.1 pM-1 μM range are reported (16).…”

mentioning

confidence: 99%

In vitro selection with artificial expanded genetic information systems

Sefah

Yang

Bradley

et al. 2013

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

291

250

View full text Add to dashboard Cite

show abstract

“…Proteomic technology has evolved rapidly and a novel assay based on slow off-rate modified aptamers (SOMAmers) are used as capture reagents in order to achieve highly selective protein detection for biomarker identification [127]. The SOMAmers are short, single-stranded deoxynucleotides with an ability to bind discrete molecular targets.…”

Section: -Protein Classifier In Serummentioning

confidence: 99%

Malignant pleural mesothelioma: history, controversy and future of a manmade epidemic

2015

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Asbestos is the term for a family of naturally occurring minerals that have been used on a small scale since ancient times. Industrialisation demanded increased mining and refining in the 20th century, and in 1960, Wagner, Sleggs and Marchand from South Africa linked asbestos to mesothelioma, paving the way to the current knowledge of the aetiology, epidemiology and biology of malignant pleural mesothelioma. Pleural mesothelioma is one of the most lethal cancers, with increasing incidence worldwide. This review will give some snapshots of the history of pleural mesothelioma discovery, and the body of epidemiological and biological research, including some of the controversies and unresolved questions. Translational research is currently unravelling novel circulating biomarkers for earlier diagnosis and novel treatment targets. Current breakthrough discoveries of clinically promising noninvasive biomarkers, such as the 13-protein signature, microRNAs and the BAP1 mesothelioma/cancer syndrome, are highlighted. The asbestos history is a lesson to not be repeated, but here we also review recent in vivo and in vitro studies showing that manmade carbon nanofibres could pose a similar danger to human health. This should be taken seriously by regulatory bodies to ensure thorough testing of novel materials before release in the society. @ERSpublications Malignant pleural mesothelioma is a cancer with increasing death tolls due to the past and present use of asbestos http://ow.ly/DhA2y

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“…A key advantage of our technology is that we can use the same affinity reagents (SOMAmers) for biomarker discovery and the clinical assay format. For example, we have developed a streamlined version of our SOMAmer-based assay using streptavidin-coated microtiter plates and plate washing equipment that is standard in clinical labs (Kraemer et al 2011). The streamlined platform is capable of efficiently measuring panels of a few to a few hundred proteins with performance similar to our discovery platform (Kraemer et al 2011).…”

Section: Translating Diagnostic From Discovery To Clinical Formatmentioning

confidence: 99%

“…For example, we have developed a streamlined version of our SOMAmer-based assay using streptavidin-coated microtiter plates and plate washing equipment that is standard in clinical labs (Kraemer et al 2011). The streamlined platform is capable of efficiently measuring panels of a few to a few hundred proteins with performance similar to our discovery platform (Kraemer et al 2011). In the course of developing diagnostics, we have successfully transferred diagnostic tests from the discovery platform to the streamlined platform for conducting validation studies (Kraemer et al 2011).…”

Section: Translating Diagnostic From Discovery To Clinical Formatmentioning

confidence: 99%

Slow Off-Rate Modified Aptamer Arrays for Biomarker Discovery and Diagnostic Applications

Walker

Brody

Gold

2012

Microarrays in Diagnostics and Biomarker Development

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The fields of "omics" have fundamentally influenced how we do research, how we understand biological systems, and how we search for biomarkers for new diagnostics. Omics is increasingly appreciated for generating hypotheses by enabling unbiased discovery of new phenomena to guide further experiments (Brody et al. 2010;Glass 2010;Kell and Oliver 2004;Lander 2010;Nabel 2009).In 1997, we concluded that, of all the omics, proteomics would most likely yield the most valuable biological and health information, and we set out to use aptamers (single-stranded DNA molecules with high affinity for specific proteins) to conduct unbiased proteomic measurements to interrogate biological systems and identify biomarkers of human disease in order to advance personalized medicine with new diagnostics and treatments. Our goal was to transform proteomics in the way that DNA microarrays transformed genomics. Over the past few years, we have made great progress, and microarrays have played an important role. For highly multiplexed measurements, microarrays elegantly solve the problem of multiplexing through spatial addressing. Advancing microarray technology has been key to advances in omics sciences, and today a large variety of technologies enable applications, from inexpensive microarrays for tens of DNA targets that enable the latest crop of molecular diagnostics (i.e., nucleic acid-based diagnostics) to high-performance microarrays with millions of features for quantitative transcriptomics.

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From SOMAmer-Based Biomarker Discovery to Diagnostic and Clinical Applications: A SOMAmer-Based, Streamlined Multiplex Proteomic Assay

Cited by 249 publications

References 12 publications

In vitro selection with artificial expanded genetic information systems

In vitro selection with artificial expanded genetic information systems

Malignant pleural mesothelioma: history, controversy and future of a manmade epidemic

Slow Off-Rate Modified Aptamer Arrays for Biomarker Discovery and Diagnostic Applications

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